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Kay M Crossley - One of the best experts on this subject based on the ideXlab platform.
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quality of life impairments after hip arthroscopy in people with hip Chondropathy
Journal of Hip Preservation Surgery, 2016Co-Authors: Stephanie R Filbay, Joanne L Kemp, Kay M Crossley, Ilana N AckermanAbstract:Many young individuals undergoing hip arthroscopic surgery have hip Chondropathy. The impact of mild or more severe hip Chondropathy 1-2 years following arthroscopy is poorly understood. The purpose of this study was to (i) compare health-related quality of life (HRQoL), anxiety and depression scores between people who underwent arthroscopic treatment for hip Chondropathy 1-2 years previously and pain-free controls; (ii) compare HRQoL, hip-related quality of life (QoL) and anxiety/depression scores in people with mild versus severe hip Chondropathy and (iii) compare hip-related QoL items between Chondropathy groups. The Hip disability and Osteoarthritis Outcome Score (HOOS), International Hip Outcome Tool (iHOT-33), EuroQol-5D and Hospital Anxiety and Depression Scale (HADS) were compared between 71 individuals aged 18-60 years following arthroscopic treatment for hip chondroplasty (12-24 months previously) and 46 healthy controls. Comparisons were also performed between people with mild (Outerbridge grade 1-2) and severe (Outerbridge grade 3-4) hip Chondropathy. Participants following arthroscopic treatment for hip chondroplasty reported worse HRQoL, hip-related QoL and anxiety, compared with pain-free controls (all P < 0.05), but no difference in self-care (P = 0.20). There were differences between mild and severe Chondropathy groups for pain during sport/recreation [median (IQR) 20 (5-80) versus 60 (25-90) P = 0.01), pain after activity (40 (20-75) versus 75 (50-90) P = 0.01), difficulty maintaining fitness (30 (10-70) versus 75 (35-85) P = 0.02) and reduced hip confidence. Hip Chondropathy was associated with significant QoL impairment, with severe Chondropathy associated with the greatest impairment. The identification of specific areas of QoL impairment provides avenues to target rehabilitation and support.
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hip Chondropathy at arthroscopy prevalence and relationship to labral pathology femoroacetabular impingement and patient reported outcomes
British Journal of Sports Medicine, 2014Co-Authors: Joanne L Kemp, Michael Makdissi, Anthony G Schache, Michael G Pritchard, T C B Pollard, Kay M CrossleyAbstract:Background This study aimed to describe Chondropathy prevalence in adults who had undergone hip arthroscopy for hip pain. The relationships between Chondropathy severity and (1) participant characteristics; and (2) patient-reported outcomes (PROs) at initial assessment (∼18 months postsurgery) and over a further 12 months (∼30 months postsurgery) were evaluated. Finally, the relationships between Chondropathy and coexisting femoroacetabular impingement (FAI) and labral pathology at the time of surgery were evaluated. Methods 100 consecutive patients (36±12 years) who underwent hip arthroscopy 18 months previously participated. Hip Osteoarthritis and Disability Outcome Score (HOOS) and International Hip Outcome Tool (iHOT-33) data were collected prospectively at 18 months postsurgery and at 30 months postsurgery. Surgical data were collected retrospectively. Participants were grouped: Outerbridge grade 0, no Chondropathy; Outerbridge grade I–II, mild Chondropathy; Outerbridge III–IV, severe Chondropathy. The presence of FAI or labral pathology was noted. Results The prevalence of Chondropathy (≥grade I) at hip arthroscopy was 72%. Participants with severe Chondropathy were significantly worse for all HOOS subscales and the iHOT-33 at 18 months postsurgery (HOOS-symptoms (p=0.017); HOOS-pain (p=0.024); HOOS-activity (p=0.009); HOOS-sport (p=0.004); HOOS-quality-of-life (p=0.006); iHOT-33 (p=0.013)) than those with no Chondropathy. At 12-month follow-up, HOOS-quality-of-life in those without Chondropathy was the only PRO that improved. Relative risk of coexisting Chondropathy with labral pathology or FAI was 40%. Conclusions Chondropathy was prevalent, and associated with increasing age, coexisting labral pathology or FAI. Severe Chondropathy was associated with worse pain and function at 18 months postsurgery. Little improvements were observed in participants over a further 12 months, regardless of Chondropathy status.
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impairment of dynamic single leg balance performance in individuals with hip Chondropathy
Arthritis Care and Research, 2014Co-Authors: Anna L Hatton, Joanne L Kemp, Sandra G Brauer, Ross A Clark, Kay M CrossleyAbstract:Objective Impaired balance control has been reported in the elderly with hip osteoarthritis, yet this relationship has not been explored in young adults with hip Chondropathy. This study aimed to determine whether people with hip Chondropathy demonstrated impaired balance ability during a dynamic single-leg squat with eyes open (SquatEO) and a single-leg standing task with eyes closed (StandEC) and whether hip range of motion (ROM) and hip muscle strength were correlated with balance measures in adults with hip Chondropathy. Methods Sixty-three adults with hip Chondropathy and 60 controls performed 2 tasks: SquatEO and StandEC while standing on a Nintendo Wii Balance Board. Center of pressure (COP) movement in mediolateral and anteroposterior directions was extracted. Hip ROM and muscle strength were measured with an inclinometer and dynamometer. Data were analyzed using an analysis of covariance and stepwise multiple regression model. Results During SquatEO, greater COP mediolateral range (P = 0.023) and anteroposterior SD (P = 0.043) were observed in those with hip Chondropathy compared to controls. No significant between-group differences were observed for StandEC. Hip external rotation ROM was significantly associated with mediolateral range during SquatEO. Conclusion Dynamic single-leg balance squat performance is reduced in people with hip Chondropathy compared to healthy adults, but static single-leg standing balance is not. This may be reflective of reduced control of dynamic movements. Those with greater hip joint external rotation ROM appear to have worse single-leg squat balance performance. Further investigation into balance deficits associated with hip disease is necessary to establish early identification strategies and a tailored approach to rehabilitation.
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dynamic single leg balance performance is impaired in individuals with hip Chondropathy
Osteoarthritis and Cartilage, 2013Co-Authors: Anna L Hatton, Joanne L Kemp, Sandra G Brauer, Ross A Clark, Kay M CrossleyAbstract:were reduced by surgery while the non-operated knee remained unchanged (Figures 1 & 2). The limb differences in peak 1 and 2 of KAM were significant (p1⁄40.0028 and 0.005, respectively). Both before and after surgery, the non-operated knee did not differ significantly from healthy control in KVA or KAM. The knee was significantly worse than controls in pain scores and spatiotemporal parameters. Conclusions: The study's findings suggest that gait patterns in the nonoperated knee may not change after surgery. The study confirms that there is a limb asymmetry after surgery, with the non-operated limb bearing greater loads than the operated limb, but suggests that the asymmetry likely results from improvements in the operated knee rather than deterioration in the non-operated knee. As a whole, the findings indicated that the surgery itself might not be the catalyst for higher loading patterns postoperatively. Nevertheless, the non-operated knee may still be at risk for OA after surgery due to the limb asymmetry and the persistent higher levels of KAM. Clinicians should consider this when prescribing therapy to patients postoperatively. There should be a focus on caring for the non-operated knee in addition to the operated knee.
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people with Chondropathy have greater physical impairments than those without following hip arthroscopy
Osteoarthritis and Cartilage, 2013Co-Authors: Joanne L Kemp, Michael Makdissi, Anthony G Schache, M G Pritchard, Kay M CrossleyAbstract:improvements in single leg balance in the NEXA group (p<0.001). Improvements in pain and function in both groups exceeded minimally clinically important differences. The number (%) of participants reporting overall improvement following treatment was similar in both groups: 27/47 (57%) in NEXA and 27/45 (60%) in QS (relative risk 0.94 (95% CI 0.67-1.33) p1⁄40.74). Conclusions: A NEXA program did not result in greater reductions in knee load or pain or improvements in function compared to a traditional QS program. As both exercise programs provided clinically important changes in pain and function, this suggests that either program can be used in this patient population. However, as neither reduced knee load they are unlikely to slow disease progression in those with varus malalignment
Joanne L Kemp - One of the best experts on this subject based on the ideXlab platform.
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quality of life impairments after hip arthroscopy in people with hip Chondropathy
Journal of Hip Preservation Surgery, 2016Co-Authors: Stephanie R Filbay, Joanne L Kemp, Kay M Crossley, Ilana N AckermanAbstract:Many young individuals undergoing hip arthroscopic surgery have hip Chondropathy. The impact of mild or more severe hip Chondropathy 1-2 years following arthroscopy is poorly understood. The purpose of this study was to (i) compare health-related quality of life (HRQoL), anxiety and depression scores between people who underwent arthroscopic treatment for hip Chondropathy 1-2 years previously and pain-free controls; (ii) compare HRQoL, hip-related quality of life (QoL) and anxiety/depression scores in people with mild versus severe hip Chondropathy and (iii) compare hip-related QoL items between Chondropathy groups. The Hip disability and Osteoarthritis Outcome Score (HOOS), International Hip Outcome Tool (iHOT-33), EuroQol-5D and Hospital Anxiety and Depression Scale (HADS) were compared between 71 individuals aged 18-60 years following arthroscopic treatment for hip chondroplasty (12-24 months previously) and 46 healthy controls. Comparisons were also performed between people with mild (Outerbridge grade 1-2) and severe (Outerbridge grade 3-4) hip Chondropathy. Participants following arthroscopic treatment for hip chondroplasty reported worse HRQoL, hip-related QoL and anxiety, compared with pain-free controls (all P < 0.05), but no difference in self-care (P = 0.20). There were differences between mild and severe Chondropathy groups for pain during sport/recreation [median (IQR) 20 (5-80) versus 60 (25-90) P = 0.01), pain after activity (40 (20-75) versus 75 (50-90) P = 0.01), difficulty maintaining fitness (30 (10-70) versus 75 (35-85) P = 0.02) and reduced hip confidence. Hip Chondropathy was associated with significant QoL impairment, with severe Chondropathy associated with the greatest impairment. The identification of specific areas of QoL impairment provides avenues to target rehabilitation and support.
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hip Chondropathy at arthroscopy prevalence and relationship to labral pathology femoroacetabular impingement and patient reported outcomes
British Journal of Sports Medicine, 2014Co-Authors: Joanne L Kemp, Michael Makdissi, Anthony G Schache, Michael G Pritchard, T C B Pollard, Kay M CrossleyAbstract:Background This study aimed to describe Chondropathy prevalence in adults who had undergone hip arthroscopy for hip pain. The relationships between Chondropathy severity and (1) participant characteristics; and (2) patient-reported outcomes (PROs) at initial assessment (∼18 months postsurgery) and over a further 12 months (∼30 months postsurgery) were evaluated. Finally, the relationships between Chondropathy and coexisting femoroacetabular impingement (FAI) and labral pathology at the time of surgery were evaluated. Methods 100 consecutive patients (36±12 years) who underwent hip arthroscopy 18 months previously participated. Hip Osteoarthritis and Disability Outcome Score (HOOS) and International Hip Outcome Tool (iHOT-33) data were collected prospectively at 18 months postsurgery and at 30 months postsurgery. Surgical data were collected retrospectively. Participants were grouped: Outerbridge grade 0, no Chondropathy; Outerbridge grade I–II, mild Chondropathy; Outerbridge III–IV, severe Chondropathy. The presence of FAI or labral pathology was noted. Results The prevalence of Chondropathy (≥grade I) at hip arthroscopy was 72%. Participants with severe Chondropathy were significantly worse for all HOOS subscales and the iHOT-33 at 18 months postsurgery (HOOS-symptoms (p=0.017); HOOS-pain (p=0.024); HOOS-activity (p=0.009); HOOS-sport (p=0.004); HOOS-quality-of-life (p=0.006); iHOT-33 (p=0.013)) than those with no Chondropathy. At 12-month follow-up, HOOS-quality-of-life in those without Chondropathy was the only PRO that improved. Relative risk of coexisting Chondropathy with labral pathology or FAI was 40%. Conclusions Chondropathy was prevalent, and associated with increasing age, coexisting labral pathology or FAI. Severe Chondropathy was associated with worse pain and function at 18 months postsurgery. Little improvements were observed in participants over a further 12 months, regardless of Chondropathy status.
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impairment of dynamic single leg balance performance in individuals with hip Chondropathy
Arthritis Care and Research, 2014Co-Authors: Anna L Hatton, Joanne L Kemp, Sandra G Brauer, Ross A Clark, Kay M CrossleyAbstract:Objective Impaired balance control has been reported in the elderly with hip osteoarthritis, yet this relationship has not been explored in young adults with hip Chondropathy. This study aimed to determine whether people with hip Chondropathy demonstrated impaired balance ability during a dynamic single-leg squat with eyes open (SquatEO) and a single-leg standing task with eyes closed (StandEC) and whether hip range of motion (ROM) and hip muscle strength were correlated with balance measures in adults with hip Chondropathy. Methods Sixty-three adults with hip Chondropathy and 60 controls performed 2 tasks: SquatEO and StandEC while standing on a Nintendo Wii Balance Board. Center of pressure (COP) movement in mediolateral and anteroposterior directions was extracted. Hip ROM and muscle strength were measured with an inclinometer and dynamometer. Data were analyzed using an analysis of covariance and stepwise multiple regression model. Results During SquatEO, greater COP mediolateral range (P = 0.023) and anteroposterior SD (P = 0.043) were observed in those with hip Chondropathy compared to controls. No significant between-group differences were observed for StandEC. Hip external rotation ROM was significantly associated with mediolateral range during SquatEO. Conclusion Dynamic single-leg balance squat performance is reduced in people with hip Chondropathy compared to healthy adults, but static single-leg standing balance is not. This may be reflective of reduced control of dynamic movements. Those with greater hip joint external rotation ROM appear to have worse single-leg squat balance performance. Further investigation into balance deficits associated with hip disease is necessary to establish early identification strategies and a tailored approach to rehabilitation.
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dynamic single leg balance performance is impaired in individuals with hip Chondropathy
Osteoarthritis and Cartilage, 2013Co-Authors: Anna L Hatton, Joanne L Kemp, Sandra G Brauer, Ross A Clark, Kay M CrossleyAbstract:were reduced by surgery while the non-operated knee remained unchanged (Figures 1 & 2). The limb differences in peak 1 and 2 of KAM were significant (p1⁄40.0028 and 0.005, respectively). Both before and after surgery, the non-operated knee did not differ significantly from healthy control in KVA or KAM. The knee was significantly worse than controls in pain scores and spatiotemporal parameters. Conclusions: The study's findings suggest that gait patterns in the nonoperated knee may not change after surgery. The study confirms that there is a limb asymmetry after surgery, with the non-operated limb bearing greater loads than the operated limb, but suggests that the asymmetry likely results from improvements in the operated knee rather than deterioration in the non-operated knee. As a whole, the findings indicated that the surgery itself might not be the catalyst for higher loading patterns postoperatively. Nevertheless, the non-operated knee may still be at risk for OA after surgery due to the limb asymmetry and the persistent higher levels of KAM. Clinicians should consider this when prescribing therapy to patients postoperatively. There should be a focus on caring for the non-operated knee in addition to the operated knee.
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people with Chondropathy have greater physical impairments than those without following hip arthroscopy
Osteoarthritis and Cartilage, 2013Co-Authors: Joanne L Kemp, Michael Makdissi, Anthony G Schache, M G Pritchard, Kay M CrossleyAbstract:improvements in single leg balance in the NEXA group (p<0.001). Improvements in pain and function in both groups exceeded minimally clinically important differences. The number (%) of participants reporting overall improvement following treatment was similar in both groups: 27/47 (57%) in NEXA and 27/45 (60%) in QS (relative risk 0.94 (95% CI 0.67-1.33) p1⁄40.74). Conclusions: A NEXA program did not result in greater reductions in knee load or pain or improvements in function compared to a traditional QS program. As both exercise programs provided clinically important changes in pain and function, this suggests that either program can be used in this patient population. However, as neither reduced knee load they are unlikely to slow disease progression in those with varus malalignment
Tl Vincent - One of the best experts on this subject based on the ideXlab platform.
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does pain at an earlier stage of Chondropathy protect female mice from structural progression after surgically induced osteoarthritis
Arthritis & Rheumatism, 2020Co-Authors: Isabell S Von Loga, S-ll Chia, Vicky Batchelor, C Driscoll, A Burleigh, B Stott, J Miotlazarebska, David M Riley, Francesco Dellaccio, Tl VincentAbstract:OBJECTIVE Female C57BL/6 mice exhibit less severe Chondropathy than male mice. This study was undertaken to test the robustness of this observation and explore underlying mechanisms. METHODS Osteoarthritis was induced in male and female C57BL/6 or DBA/1 mice (n = 6-15 per group) by destabilization of the medial meniscus (DMM) or partial meniscectomy (PMX). Some mice were ovariectomized (OVX) (n = 30). In vivo repair after focal cartilage defect or joint immobilization (sciatic neurectomy) following DMM was assessed. Histologic analysis, evaluation of gene expression in whole knees, and behavioral analysis using Laboratory Animal Behavior Observation Registration and Analysis System (LABORAS) and Linton incapacitance testing (n = 7-10 mice per group) were performed. RESULTS Female mice displayed less severe Chondropathy (20-75% reduction) across both strains and after both surgeries. Activity levels after PMX were similar for male and female mice. Some repair-associated genes were increased in female mouse joints after surgery, but no repair differences were evident in vivo. Despite reduced Chondropathy, female mice developed pain-like behavior at the same time as male mice. At the time of established pain-like behavior (10 weeks after PMX), pain-associated genes were significantly up-regulated in female mice, including Gdnf (mean ± SEM fold change 2.54 ± 0.30), Nrtn (6.71 ± 1.24), Ntf3 (1.92 ± 0.27), and Ntf5 (2.89 ± 0.48) (P < 0.01, P < 0.01, P < 0.05, and P < 0.001, respectively, versus male mice). Inflammatory genes were not regulated in painful joints in mice of either sex. CONCLUSION We confirm strong structural joint protection in female mice that is not due to activity or intrinsic repair differences. Female mice develop pain at the same time as males, but induce a distinct set of neurotrophins. We speculate that heightened pain sensitivity in female mice protects the joint by preventing overuse.
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Does Pain at an Earlier Stage of Chondropathy Protect Female Mice Against Structural Progression After Surgically Induced Osteoarthritis?
'Wiley', 2020Co-Authors: Is ,von Loga, Driscoll C, Burleigh A, S-ll Chia, Stott B, Miotla-zarebska J, Riley D, Dell'accio F, Tl VincentAbstract:OBJECTIVE: Female C57BL/6 mice exhibit less severe Chondropathy than male mice. This study was undertaken to test the robustness of this observation and explore underlying mechanisms. METHODS: Osteoarthritis was induced in male and female C57BL/6 or DBA/1 mice (n = 6-15 per group) by destabilization of the medial meniscus (DMM) or partial meniscectomy (PMX). Some mice were ovariectomized (OVX) (n = 30). In vivo repair after focal cartilage defect or joint immobilization (sciatic neurectomy) following DMM was assessed. Histologic analysis, evaluation of gene expression in whole knees, and behavioral analysis using Laboratory Animal Behavior Observation Registration and Analysis System (LABORAS) and Linton incapacitance testing (n = 7-10 mice per group) were performed. RESULTS: Female mice displayed less severe Chondropathy (20-75% reduction) across both strains and after both surgeries. Activity levels after PMX were similar for male and female mice. Some repair-associated genes were increased in female mouse joints after surgery, but no repair differences were evident in vivo. Despite reduced Chondropathy, female mice developed pain-like behavior at the same time as male mice. At the time of established pain-like behavior (10 weeks after PMX), pain-associated genes were significantly up-regulated in female mice, including Gdnf (mean ± SEM fold change 2.54 ± 0.30), Nrtn (6.71 ± 1.24), Ntf3 (1.92 ± 0.27), and Ntf5 (2.89 ± 0.48) (P < 0.01, P < 0.01, P < 0.05, and P < 0.001, respectively, versus male mice). Inflammatory genes were not regulated in painful joints in mice of either sex. CONCLUSION: We confirm strong structural joint protection in female mice that is not due to activity or intrinsic repair differences. Female mice develop pain at the same time as males, but induce a distinct set of neurotrophins. We speculate that heightened pain sensitivity in female mice protects the joint by preventing overuse
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ccl2 and ccr2 regulate pain related behaviour and early gene expression in post traumatic murine osteoarthritis but contribute little to Chondropathy
Osteoarthritis and Cartilage, 2017Co-Authors: Miotla J Zarebska, C Driscoll, A Burleigh, B Stott, A Chanalaris, Rachel E Miller, A M Malfait, Tl VincentAbstract:Summary Objective The role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator of inflammation is the chemokine CCL2, primarily responsible for attracting monocytes to sites of injury. We investigated the role of CCL2 and its receptor CCR2 in experimental OA. Design OA was induced in 10 weeks old male wild type (WT), Ccl2 −/− and Ccr2 −/− mice, by destabilisation of the medial meniscus (DMM). RNA was extracted from whole joints at 6 h and 7 days post-surgery and examined by reverse transcription polymerase chain reaction (RT-PCR). Gene expression changes between naive and DMM-operated mice were compared. Chondropathy scores, from mice at 8, 12, 16 and 20 weeks post DMM were calculated using modified Osteoarthritis Research Society International (OARSI) grading systems. Changes in hind paw weight distribution, as a measure of pain, were assessed by Linton incapacitance. Results Absence of CCL2 strongly suppressed (>90%) selective inflammatory response genes in the joint 6 h post DMM, including arginase 1, prostaglandin synthase 2, nitric oxide synthase 2 and inhibin A. IL6, MMP3 and tissue inhibitor of metalloproteinase 1 were also significantly suppressed. Similar trends were also observed in the absence of CCR2. A lower average Chondropathy score was observed in both Ccl2 −/− and Ccr2 −/− mice at 12, 16 and 20 weeks post DMM compared with WT mice, but this was only statistically significant at 20 weeks in Ccr2 −/− mice. Pain-related behaviour in Ccl2 −/− and Ccr2 −/− mice post DMM was delayed in onset. Conclusion The CCL2/CCR2 axis plays an important role in the development of pain in murine OA, but contributes little to cartilage damage.
David A Walsh - One of the best experts on this subject based on the ideXlab platform.
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(A) CB2 receptor mRNA expression in the lumbar spinal cord was negatively correlated with macroscopic knee Chondropathy scores. (B) GFAP mRNA expression in the lumbar spinal cord was positively correlated with macroscopic knee Chondropathy scores. Da
2013Co-Authors: James J. Burston, Devi Rani Sagar, Pin Shao, Mingfeng Bai, Emma King, Louis Brailsford, Jenna M. Turner, Gareth J. Hathway, Andrew J. Bennett, David A WalshAbstract:(A) CB2 receptor mRNA expression in the lumbar spinal cord was negatively correlated with macroscopic knee Chondropathy scores. (B) GFAP mRNA expression in the lumbar spinal cord was positively correlated with macroscopic knee Chondropathy scores. Data are expressed as mean (normalised to beta actin) ± SEM, statistical analysis (n = 11 separate spinal cord cases). Data were analysed with either a Pearson correlation or Spearman correlation depending on whether data passed normality testing.
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increased vascular penetration and nerve growth in the meniscus a potential source of pain in osteoarthritis
Annals of the Rheumatic Diseases, 2011Co-Authors: Sadaf Ashraf, Helen Wibberley, P I Mapp, R Hill, D Wilson, David A WalshAbstract:Objectives Meniscal damage is a recognised feature of knee osteoarthritis (OA), although its clinical relevance remains uncertain. This study describes vascular penetration and nerve growth in human menisci, providing a potential mechanism for the genesis of pain in knee OA. Methods Menisci obtained post mortem were screened on the basis of high or low macroscopic tibiofemoral Chondropathy as a measure of the presence and degree of OA. Forty cases (20 per group) were selected for the study of meniscal vascularity, and 16 (eight per group) for the study of meniscal innervation. Antibodies directed against α-actin and calcitonin gene-related peptide (CGRP) were used to localise blood vessels and nerves by histochemistry. Image analysis was used to compare vascular and nerve densities between groups. Data are presented as median (IQR). Results Menisci from knees with high Chondropathy displayed degeneration of collagen bundles in their outer regions, which were more vascular than the inner regions, with an abrupt decrease in vascularity at the fibrocartilage junction. Vascular densities were increased in menisci from the high compared with low Chondropathy group both in the synovium (3.8% (IQR 2.6–5.2), 2.0% (IQR 1.4–2.9), p=0.002) and at the fibrocartilage junction (2.3% (IQR 1.7–3.1), 1.1% (IQR 0.8–1.9), p=0.003), with a greater density of perivascular sensory nerve profiles in the outer region (high Chondropathy group, 144 nerve profiles/mm2 (IQR 134–189); low Chondropathy group, 119 nerve profiles/mm2 (IQR 104–144), p=0.049). Conclusion Tibiofemoral Chondropathy is associated with altered matrix structure, increased vascular penetration, and increased sensory nerve densities in the medial meniscus. The authors suggest therefore that angiogenesis and associated sensory nerve growth in menisci may contribute to pain in knee OA.
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effects of a metalloproteinase inhibitor on osteochondral angiogenesis Chondropathy and pain behavior in a rat model of osteoarthritis
Osteoarthritis and Cartilage, 2010Co-Authors: P I Mapp, David A Walsh, Jonathan Bowyer, Rose A MaciewiczAbstract:Summary Objective To investigate the effects of a matrix metalloproteinase (MMP) inhibitor on joint pathology and pain behavior in the rat meniscal transection (MNX) model of osteoarthritis (OA) and evaluate which aspects of structural disease modification contribute to symptom improvement. Methods OA pathology was induced in male Lewis rats, by transecting the medial collateral ligament with (MNX) or without (SHAM) a full thickness cut through the meniscus. MNX animals were orally administered an equipotent MMP 2, 8, 9, 12, 13 inhibitor (0.25, 1 and 5mg/kg/day) or vehicle from day 1. Chondropathy, osteophytosis, osteochondral vascularity were assessed from toluidine blue stained coronal sections of the total knee joint and weight-bearing asymmetry by incapacitance. Group differences were evaluated using 1-way analysis of variance (ANOVA) and associations as Spearman's correlation coefficients. Results Treatment with the MMP inhibitor reduced weight-bearing asymmetry from day 14 onwards, and attenuated Chondropathy (both P P r =−0.89, P P Conclusion Here we show that treatment with a MMP inhibitor reduces joint damage, osteochondral angiogenesis and behavioral evidence of pain. The association between osteochondral angiogenesis and pain behavior may be explained by perivascular nerve growth or stimulation of subchondral nerves following loss of osteochondral integrity. Our data suggest that targeting angiogenesis may have utility in the treatment of pain associated with structural damage in OA.
Walsh, David A. - One of the best experts on this subject based on the ideXlab platform.
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Associations of symptomatic knee OA with histopathologic features in subchondral bone
'Wiley', 2019Co-Authors: Mcwilliams, Daniel F., Shahtaheri Seyed, Walsh, David A., Aso Koji, Wilson Deborah, Hill RogerAbstract:© 2019, American College of Rheumatology Objective: Subchondral bone and the osteochondral junction are thought to contribute to osteoarthritis (OA) knee pain. We undertook this study to identify osteochondral pathologies specifically associated with symptomatic human knee OA. Methods: Medial tibial plateau samples from 2 groups of subjects (n = 31 per group) were matched for macroscopic Chondropathy scores. The symptomatic Chondropathy group had undergone total knee replacement for OA knee pain, at which time specimens of the medial tibial plateau were obtained. The asymptomatic Chondropathy group included subjects who died of unrelated illness (specimens were obtained at postmortem examination) and who had not previously sought help for knee pain. OA histopathology, immunoreactivity for nerve growth factor (NGF) and CD68 (macrophages), tartrate-resistant acid phosphatase–positive subchondral osteoclasts, and synovitis were compared between groups. Results: Mankin scores, subchondral bone density, and subchondral CD68-immunoreactive macrophage infiltration were similar between the 2 groups. NGF-like immunoreactivity was found in subchondral mononuclear cells and osteoclasts, as well as in chondrocytes. NGF in osteochondral channels and osteoclast densities in subchondral bone were higher in the symptomatic Chondropathy group than in the asymptomatic Chondropathy group (P < 0.01 and P = 0.02, respectively), as were synovitis scores (P < 0.01). Osteochondral pathology was not significantly associated with synovitis score. The differences in NGF expression and in osteoclast density remained significant after adjustment for age and synovitis score (P = 0.01 and P = 0.04, respectively). Osteochondral NGF and osteoclast densities, together with synovitis scores, explained ~28% of sample allocation to symptomatic or asymptomatic groups. Conclusion: Subchondral pathology was associated with symptomatic knee OA, independent of Chondropathy and synovitis. Increased NGF expression in osteochondral channels and increased osteoclast density appear to be key features associated with bone pain in knee OA
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Molecular expression patterns in the synovium and their association with advanced symptomatic knee osteoarthritis
'Elsevier BV', 2018Co-Authors: Wyatt, Laura A., Wilson Deborah, Hill Roger, Scammell, Brigitte E., Nwosu, Lilian N., Spendlove Ian, Bennett, Andrew J., Walsh, David A.Abstract:Objective: Osteoarthritis (OA) is a major source of knee pain. Mechanisms of OA knee pain are incompletely understood but include synovial pathology. We aimed to identify molecular expression patterns in the synovium associated with symptomatic knee OA.Design: Snap frozen synovia were from people undergoing total knee replacement (TKR) for advanced OA, or from post-mortem (PM) cases who had not sought help for knee pain. Associations with OA symptoms were determined using discovery and validation samples, each comprising TKR and post mortem (PM) cases matched for Chondropathy (Symptomatic or Asymptomatic Chondropathy). Associations with OA were determined by comparing age matched TKR and PM control cases. Real-time quantitative PCR for 96 genes involved in inflammation and nerve sensitisation used TaqMan® Array Cards in discovery and validation samples, and protein expression for replicated genes was quantified using Luminex bead assay.Results: Eight genes were differentially expressed between asymptomatic and symptomatic Chondropathy cases and replicated between discovery and validation samples (P3-fold change). Of these, matrix metalloprotease (MMP)-1 was also increased whereas interleukin-1 receptor 1 (IL1R1) and vascular endothelial growth factor (VEGF) were decreased at the protein level in the synovium of symptomatic compared to asymptomatic Chondropathy cases. MMP1 protein expression was also increased in OA compared to PM controls.Conclusion: Associations of symptomatic OA may suggest roles of MMP1 expression and IL1R1 and VEGF pathways in OA pain. Better understanding of which inflammation-associated molecules mediate OA pain should inform refinement of existing therapies and development of new treatments
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Histopathological subgroups in knee osteoarthritis
'Elsevier BV', 2016Co-Authors: Wyatt L.a., Mapp Paul, Scammell, Brigitte E., Morerton B.j., Wilson D., Hill R., Ferguson Eamonn, Walsh, David A.Abstract:Objective: Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features. Design: Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations. A ‘Chondropathy/osteophyte’ group (n = 217) was classified as PM cases with osteophytes or macroscopic medial tibiofemoral Chondropathy lesions ≥grade 3 to represent pre-surgical (early) OA. ‘Non-arthritic’ controls (n = 48) were identified from the remaining PM cases. Mankin histopathological scores were subjected to Rasch analysis and supplemented with histopathological scores for subchondral bone marrow replacement and synovitis. Item weightings were derived by principle components analysis (PCA). Histopathological subgroups were sought using latent class analysis (LCA). Results: Chondropathy, synovitis and osteochondral pathology were each associated with OA at arthroplasty, but each was also identified in some ‘non-arthritic’ controls. Tidemark breaching in the Chondropathy/osteophyte group was greater than in non-arthritic controls. Three histopathological subgroups were identified, characterised as ‘mild OA’, or ‘severe OA’ with mild or moderate/severe synovitis. Conclusions: Presence and severity of synovitis helps define distinct histopathological OA subgroups. The absence of a discrete ‘normal’ subgroup indicates a pathological continuum between normality and OA status. Identifying specific pathological processes and their clinical correlates in OA subgroups has potential to accelerate the development of more effective therapies
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Structural associations of symptomatic knee osteoarthritis
'Wiley', 2014Co-Authors: Stoppiello, Laura A., Wilson Deborah, Hill Roger, Mapp Paul, Scammell, Brigitte E., Walsh, David A.Abstract:Objective Structural changes of osteoarthritis (OA) may occur in the absence of pain. In this study, we aimed to identify histopathologic features that are associated with symptomatic knee OA. Methods Medial tibial plateaus and synovium samples were obtained at the time of total knee replacement (TKR) surgery for OA (advanced OA group) or were obtained postmortem from subjects who had not sought medical attention for knee pain during the last year of life (non-OA control group). To identify features of OA, we compared the patients with advanced OA with the age-matched non-OA controls (n = 26 per group). To identify OA features associated with symptoms, we compared two additional groups of subjects who were matched for severity of Chondropathy (n = 29 per group): patients undergoing TKR for symptomatic OA (symptomatic Chondropathy group) and postmortem subjects with similar severity of Chondropathy who were asymptomatic during the last year of life (asymptomatic Chondropathy group). The histologic features of the samples were graded, and immunoreactivities for macrophages (CD68) and nerve growth factor (NGF) in the synovium were quantified. The cellular localization of synovial NGF was determined by double immunofluorescence analysis. Results Advanced OA cases displayed more severe changes in the synovium (synovitis, increased synovial NGF, and CD68-immunoreactive macrophages) and cartilage (loss of cartilage surface integrity, loss of proteoglycan, tidemark breaching, and alterations in chondrocyte morphology) than did the non-OA controls. Synovial NGF was localized predominantly to fibroblasts and to some macrophages. The symptomatic Chondropathy group displayed greater levels of synovitis, synovial NGF, and loss of cartilage integrity, in addition to alterations in chondrocyte morphology, than did the asymptomatic Chondropathy group (P < 0.05 for each comparison). Conclusion Synovitis, increased synovial NGF, alterations in chondrocyte morphology, and loss of cartilage integrity are features of knee OA that may be associated with symptoms
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Structural Associations of Symptomatic Knee Osteoarthritis: Structural Associations of Symptomatic Knee OA
'Wiley', 2014Co-Authors: Stoppiello, Laura A., Wilson Deborah, Hill Roger, Mapp Paul, Scammell, Brigitte E., Walsh, David A.Abstract:ObjectiveStructural changes of osteoarthritis (OA) may occur in the absence of pain. In this study, we aimed to identify histopathologic features that are associated with symptomatic knee OA.MethodsMedial tibial plateaus and synovium samples were obtained at the time of total knee replacement (TKR) surgery for OA (advanced OA group) or were obtained postmortem from subjects who had not sought medical attention for knee pain during the last year of life (non-OA control group). To identify features of OA, we compared the patients with advanced OA with the age-matched non-OA controls (n = 26 per group). To identify OA features associated with symptoms, we compared two additional groups of subjects who were matched for severity of Chondropathy (n = 29 per group): patients undergoing TKR for symptomatic OA (symptomatic Chondropathy group) and postmortem subjects with similar severity of Chondropathy who were asymptomatic during the last year of life (asymptomatic Chondropathy group). The histologic features of the samples were graded, and immunoreactivities for macrophages (CD68) and nerve growth factor (NGF) in the synovium were quantified. The cellular localization of synovial NGF was determined by double immunofluorescence analysis.ResultsAdvanced OA cases displayed more severe changes in the synovium (synovitis, increased synovial NGF, and CD68-immunoreactive macrophages) and cartilage (loss of cartilage surface integrity, loss of proteoglycan, tidemark breaching, and alterations in chondrocyte morphology) than did the non-OA controls. Synovial NGF was localized predominantly to fibroblasts and to some macrophages. The symptomatic Chondropathy group displayed greater levels of synovitis, synovial NGF, and loss of cartilage integrity, in addition to alterations in chondrocyte morphology, than did the asymptomatic Chondropathy group (P < 0.05 for each comparison).ConclusionSynovitis, increased synovial NGF, alterations in chondrocyte morphology, and loss of cartilage integrity are features of knee OA that may be associated with symptoms