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Kenji Takahashi - One of the best experts on this subject based on the ideXlab platform.

  • Volume change in infrapatellar fat pad is associated not with obesity but with Cartilage Degeneration
    Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2019
    Co-Authors: Tadashi Masaki, Kenji Takahashi, Sanshiro Hashimoto, Futoshi Ikuta, Atsuya Watanabe, Shinji Kiuchi, Tomoyuki Okuaki, Yusuke Mochizuki, Shinro Takai
    Abstract:

    Infrapatellar fat pad has been implicated in knee osteoarthritis. We examined whether infrapatellar fat pad volume is associated with quantitative Cartilage changes using magnetic resonance imaging T1ρ mapping. Fifty-eight knees of knee pain patients (19 men, 39 women, mean age 57.0 [range 29-85] years) who were conservatively managed and had >1 T1ρ mapping images taken over time were evaluated. We used three slices from the medial femoral and tibial Cartilage; areas showing T1ρ values 50 ms were designated as having Cartilage Degeneration. Cases were categorized into three groups: Improvement, No Change, and Deterioration. Fat-suppressed T2-weighted sagittal magnetic resonance images were used for measuring infrapatellar fat pad volume. Percent change in infrapatellar fat pad volume was -5.01 ± 5.66%, -2.06 ± 4.92%, and 0.05 ± 6.09% in the Improvement (n = 22), No Change (n = 22), and Deterioration (n = 14) groups, respectively, demonstrating significantly reduced infrapatellar fat pad volume in the Improvement group (p < 0.05). Multivariate regression analyses revealed that the percent change in infrapatellar fat pad volume significantly affected T1ρ change category independent of age, sex, follow-up period, baseline infrapatellar fat pad volume, and Kellgren-Lawrence grade. Infrapatellar fat pad volume and obesity or body weight change showed no correlation. Infrapatellar fat pad volume was reduced in patients with improved quantitative Cartilage assessment on magnetic resonance imaging T1ρ mapping. This is the first study demonstrating associations between quantitative Cartilage changes and infrapatellar fat pad morphological changes, suggesting a detrimental role of infrapatellar fat pad volume in articular Cartilage Degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  • medial meniscal posterior root horn radial tears correlate with Cartilage Degeneration detected by t1ρ relaxation mapping
    European Journal of Radiology, 2015
    Co-Authors: Kenji Takahashi, Sanshiro Hashimoto, Hiroshi Nakamura, Atsushi Mori, Akiko Sato, Tokifumi Majima, Shinro Takai
    Abstract:

    Abstract Objective This study aimed to identify factors on routine pulse sequence MRI associated with Cartilage Degeneration observed on T1ρ relaxation mapping. Materials and methods This study included 137 subjects with knee pain. T1ρ values were measured in the regions of interest on the surface layer of the Cartilage on mid-coronal images of the femorotibial joint. Assessment of Cartilage, subchondral bone, meniscus and ligaments was performed using routine pulse sequence MRI. Radiographic evaluation for osteoarthritis was also performed. Results Multiple regression analysis revealed posterior root/horn tears to be independent factors increasing the T1ρ values of the Cartilage in the medial compartment of the femorotibial joint. Even when adjusted for radiographically defined early-stage osteoarthritis, medial posterior meniscal radial tears significantly increased the T1ρ values. Conclusions This study showed that posterior root/horn radial tears in the medial meniscus are particularly important MRI findings associated with Cartilage Degeneration observed on T1ρ relaxation mapping. Morphological factors of the medial meniscus on MRI provide findings useful for screening early-stage osteoarthritis.

  • sat0422 medial meniscal posterior root horn radial tears are a strong predisposing factor for Cartilage Degeneration observed on t1ρ relaxation mapping
    Annals of the Rheumatic Diseases, 2014
    Co-Authors: Kenji Takahashi, Sanshiro Hashimoto, Hiroshi Nakamura, Atsushi Mori, Akiko Sato, Y Mochizuki, S Takai
    Abstract:

    Background Magnetic resonance imaging (MRI) has become a critical imaging tool for use in osteoarthritis (OA) research. Recently, the T1ρ relaxation time was developed to quantify the composition of the Cartilage matrix with respect to the proteoglycan concentration. However, the limited availability of this parameter due to the longer testing time compared to that required for the usual clinical sequences prevents its routine use in the clinical management of OA patients. Characterizing the relationship between T1ρ values and MRI findings according to prevalent sequences should be of clinical benefit. Objectives The purpose of this study was to identify factors on routine clinical sequenced MRI associated with Cartilage Degeneration observed on T1ρ relaxation mapping. Methods This study included 137 subjects with knee pain (mean: 50.6 years). Standard anteroposterior radiographs of the knee were obtained in all subjects. The Kellgren-Lawrence (KL) grade was determined by three experienced orthopaedic surgeons. MRI was performed using a 3-T scanner (Achieva 3T, Philips Medical Systems). Coronal images were acquired based on 3D T1ρ-weighted fast field echo imaging. We placed 12 regions of interest (ROIs) on the surface layer of the Cartilage on mid-coronal images of the femorotibial (FT) joint. The assessment of Cartilage, subchondral bone, meniscus and ligaments was performed using sagittal and coronal fat-suppressed T2-weighted images (T2-FFE). Meniscal scoring was carried out using a modified WORMS score for the knee. Extrusion, posterior root tears and posterior horn/root junction tears in the medial meniscus were recorded in addition to the presence of bone marrow edema and anterior cruciate ligament (ACL) tearing. A multiple regression analysis was performed to determine the factors affecting the T1ρ values of the Cartilage. Results The KL grades were as follows: 0=33 joints, 1=58 joints, 2=34 joints, 3=12 joints. The T1ρ values were significantly higher among the patients with a KL grade of 3, and no significant differences were observed between the patients with a KL grade of 0 and 1. The WORMS scores of the posterior horn of the medial meniscus were associated with the T1ρ values of the medial FT Cartilage. In particular, posterior root/horn radial tears in the medial meniscus were strong factors increasing the T1ρ values (P Conclusions Meniscal tears have been reported to be related to the progression of Cartilage loss in the knee, which can lead to osteoarthritis. This study showed that posterior root/horn radial tears in the medial meniscus depicted on MRI are particularly important findings associated with Cartilage Degeneration observed on T1ρ relaxation mapping even in patients with pre-radiological knee OA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2455

Congming Zhang - One of the best experts on this subject based on the ideXlab platform.

  • decreased histone deacetylase 4 is associated with human osteoarthritis Cartilage Degeneration by releasing histone deacetylase 4 inhibition of runt related transcription factor 2 and increasing osteoarthritis related genes a novel mechanism of human
    Arthritis Research & Therapy, 2014
    Co-Authors: Congming Zhang, Yongping Li, Shaowei Wang, Pengcui Li
    Abstract:

    Introduction To investigate if decreased histone deacetylase 4 (HDAC4) is associated with human osteoarthritis (OA) Cartilage Degeneration by releasing HDAC4 inhibition of runt-related transcription factor-2 (Runx2) resulting in increase of OA Cartilage Degeneration-related genes.

  • decreased histone deacetylase 4 is associated with human osteoarthritis Cartilage Degeneration by releasing histone deacetylase 4 inhibition of runt related transcription factor 2 and increasing osteoarthritis related genes a novel mechanism of human
    Arthritis Research & Therapy, 2014
    Co-Authors: Kun Cao, Congming Zhang, Shaowei Wang, Lei Wei, Zhiqiang Zhang, Li Guo, Changqi Sun, Xiaojuan Sun, Xiaochun Wei
    Abstract:

    To investigate if decreased histone deacetylase 4 (HDAC4) is associated with human osteoarthritis (OA) Cartilage Degeneration by releasing HDAC4 inhibition of runt-related transcription factor-2 (Runx2) resulting in increase of OA Cartilage Degeneration-related genes. The mRNA and protein levels of HDAC4, Runx2, matrix metalloproteinase (MMP)-13, Indian hedgehog (Ihh) and type X collagen were detected by performing real-time PCR (RT-PCR), western blotting and immunohistochemistry on specimens from human OA and normal Cartilage. To further explore the mechanism of regulation of Runx2 and OA-related genes by HDAC4, changes in these OA-related genes were further quantified by RT-PCR after overexpression of HDAC4 and knockdown of HDAC4 by siRNA. Runx2 and MMP-13 promoter activities were measured by dual luciferase assays. The levels of HDAC4 in the Cartilage from OA patients and healthy 40- to 60-year-old donors were decreased to 31% and 65% compared with specimens from 20- to 40-year-old healthy donors, respectively (P <0.05). Decreased HDAC4 was associated with increased Runx2 and other OA-related genes in human OA Cartilage, specifically: MMP-13, Ihh and type X collagen. Exogenous HDAC4 decreased the mRNA levels of Runx2, MMP1, MMP3, MMP-13, type X collagen, Ihh, ADAMTS-4 and -5, and increased the mRNA of type II collagen. In addition, the data also shows that overexpression of HDAC4 not only decreased the expression of interleukin (IL)-1β, Cox2 and iNos and increased the expression of aggrecan, but also partially blocked the effect of IL-1β on expression of catabolic events in human OA chondrocytes. HDAC4 also inhibited Runx2 promoter activity and MMP13 promotor activity in a dose-dependent manner. In contrast, inhibition of HDAC4 by TSA drug had an opposite effect. Our study is the first to demonstrate that decreased HDAC4 contributes, at least in part, to the pathogenesis of OA Cartilage Degeneration. Thus, HDAC4 may have chondroprotective properties by inhibiting Runx2 and OA-related genes.

Pengcui Li - One of the best experts on this subject based on the ideXlab platform.

K Y Chiu - One of the best experts on this subject based on the ideXlab platform.

  • prevent action of magnoflorine with hyaluronic acid gel from Cartilage Degeneration in anterior cruciate ligament transection induced osteoarthritis
    Biomedicine & Pharmacotherapy, 2020
    Co-Authors: Zhe Cai, Ming Hong, Kedi Yang, Tianhao Sun, Yu Feng, Huasong Zeng, K Y Chiu
    Abstract:

    According to the Chinese medicine, magnoflorine exerted significant anti-inflammatory effects and potentially promoted synthesis of proteoglycans in chondrocytes to reverse the progression of rheumatoid arthritis. However, the latent beneficial effect of magnoflorine for the treatment of traumatic osteoarthritis (OA) is still unknown. Therefore, we aim to demonstrate the efficacy of magnoflorine combined with HA-gel in attenuating Cartilage Degeneration in anterior cruciate ligament transection (ACLT) induced OA rat model. We found that the histological results showed the elevated Cartilage matrix, chondrogenic signals and chondroprogenitor cells in HA-gel + magnoflorine treatment. HA-gel + magnoflorine treatment resulted in a decreased modified Mankin's score, and a higher volume ratio of hyaline Cartilage (HC)/calcified Cartilage (CC) and HC/Sum (whole Cartilage), compared to ACLT and HA-gel groups. Furthermore, both the volume ratios of HC/Sum and HC/CC were negatively correlated with modified Mankin's scores. Finally, HA-gel + magnoflorine could significantly increase the BV/TV, Tb.Th, and decrease the Tb.Pf, Po(tot), Conn.Dn and Tb.Sp. In vitro, 50 μg/ml magnoflorine treatment could significantly increase the viability, S-phase, migration rate and chondrogenesis of chondroprogenitor cells. There were significant downregulations of MAPK/NF-κB signaling, and upregulations of chondrogenic signals in 50 μg/ml magnoflorine treatment. There were significant downregulations of proinflammatory cytokines and upregulation of IL-10 in HA-gel + magnoflorine treated group. Therefore, our study elucidated a protective effect of HA-gel + magnoflorine on attenuating Cartilage degradation and maintaining SCB stabilization in ACLT induced OA.

  • magnoflorine with hyaluronic acid gel promotes subchondral bone regeneration and attenuates Cartilage Degeneration in early osteoarthritis
    Bone, 2018
    Co-Authors: Zhe Cai, Yan Chen, Kedi Yang, Tianhao Sun, Yu Feng, C Yan, K Y Chiu
    Abstract:

    Abstract Objective To investigate efficacy of Chinese medicine magnoflorine combined with hyaluronic acid (HA)-gel in promoting subchondral bone (SCB) regeneration and attenuating Cartilage Degeneration in early osteoarthritis (OA). Methods MC3T3-E1 under magnoflorine treatment was assayed by XTT to determine cell viability. Cell proliferation was reflected through cell cycle. Osteoblast mineralization was stained by Alizarin Red. Standardized bone canal of 1 mm in diameter and 4 mm in depth was made on tibial medial plateau of 4-month-old Dunkin-Hartley spontaneous knee OA guinea pigs. Guinea pigs (n = 5/group) were treated once intra-bone canal injection of 2 μl HA-gel, 2 μl HA-gel+50 ng magnoflorine and null (Defect) respectively, except sham group. The left hind limbs were harvested for μCT scan and histopathological staining 2-month post-surgery. Results 25 μg/ml magnoflorine treatment significantly increased cell viability, S-phase and mineralization of MC3T3-E1 cells. In vivo, HA-gel + magnoflorine treatment significantly altered SCB microstructure; changes included increase in bone volume fraction (BV/TV), trabecular number (Tb.N), connectivity density (Conn.Dn), and decrease in degree of anisotropy (DA), which implied trabecular bone regeneration. Treatment also resulted in a decrease in modified Mankin's scores, and an increase in volume ratio of hyaline Cartilage (HC)/calcified Cartilage (CC) and fractal dimension (FD, roughness indicator of osteochondral conjunction), compared to Defect and HA groups. Furthermore, FD was positively associated with volume ratio of HC/CC and negatively associated with modified Mankin's scores. Finally, histological results showed that due to a faster regeneration of SCB with the HA-gel + magnoflorine treatment, the reduction of Cartilage matrix and the decreased expression of chondrogenic signals were attenuated. Conclusion Our study elucidated the potential benefits of HA-gel + magnoflorine in promoting SCB regeneration and revealed a protective effect of stimulating recovery of the SCB integrity on attenuating Cartilage degradation to prevent OA progression.

  • Cartilage Degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered tgf β signaling
    Journal of Orthopaedic Research, 2016
    Co-Authors: Weiwei Zhao, K Y Chiu, Ting Wang, Yan Chen, Victor Y L Leung, Mohammed F Shah, W W Lu
    Abstract:

    Abstract Transforming growth factor-β (TGF-β) has been demonstrated as a potential therapeutic target in osteoarthritis. However, beneficial effects of TGF-β supplement and inhibition have both been reported, suggesting characterization of the spatiotemporal distribution of TGF-β during the whole time course of osteoarthritis is important. To investigate the activity of TGF-β in osteoarthritis progression, we collected knee joints from Dunkin-Hartley (DH) guinea pigs at 3, 6, 9, and 12-month old (n = 8), which develop spontaneous osteoarthritis in a manner extraordinarily similar to humans. Via histology and micro-computed tomography (CT) analysis, we found that the joints exhibited gradual Cartilage Degeneration, subchondral plate sclerosis, and elevated bone remodeling during aging. The degenerating Cartilage showed a progressive switch of the expression of phosphorylated Smad2/3 to Smad1/5/8, suggesting dual roles of TGF-β/Smad signaling during chondrocyte terminal differentiation in osteoarthritis progression. In subchondral bone, we found that the locations and age-related changes of osterix(+) osteoprogenitors were in parallel with active TGF-β, which implied the excessive osteogenesis may link to the activity of TGF-β. Our study, therefore, suggests an association of Cartilage Degeneration and excessive bone remodeling with altered TGF-β signaling in osteoarthritis progression of DH guinea pigs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:763-770, 2016.

  • spatial and temporal changes of subchondral bone proceed to microscopic articular Cartilage Degeneration in guinea pigs with spontaneous osteoarthritis
    Osteoarthritis and Cartilage, 2013
    Co-Authors: T Wang, W W Lu, K Y Chiu
    Abstract:

    Summary Objective This study aimed to investigate the spatial and temporal subchondral bone change of Dunkin–Hartley (DH) strain guinea pigs spontaneous osteoarthritis (OA) model at early stage with three-dimensional Microfocal Computed Tomography (Micro-CT) analysis, histology and immunohistochemistry. Materials and methods Knee joints of DH and Bristol Strain 2 (BS2) guinea pigs were analyzed at 1, 2 and 3 months of age for early staged subchondral bone ultrastructure change of OA by Micro-CT and histology. And Cartilage Degeneration was monitored by histological examination. In addition, expression of Osterix was quantified by immunohistochemistry. Results Microscopic Cartilage Degeneration was not found at first 3 months in both DH and BS2 guinea pigs. Subchondral bone sclerosis with trabecular ultrastructure turnover was characterized in subchondral bone of DH guinea pigs. Increased thickness, bone mineral density with decreased porosity were defined in subchondral plate of DH guinea pigs. Subchondral trabecular bone was found to be plate-like, convex and isotropy with higher bone volume. Histology confirmed the finding of lower porosity at osteochondral junction and increased bone volume. Immunohistochemistry revealed that the early OA subchondral bone change may be due to elevated level of osteoblast differentiation. Conclusions Subchondral bone ultrastructure change occurred at early stage of OA ahead of microscopic Cartilage Degeneration, which may further impair articular Cartilage. It was possibly related to elevated level of osteoblast differentiation.

Shaowei Wang - One of the best experts on this subject based on the ideXlab platform.

  • decreased histone deacetylase 4 is associated with human osteoarthritis Cartilage Degeneration by releasing histone deacetylase 4 inhibition of runt related transcription factor 2 and increasing osteoarthritis related genes a novel mechanism of human
    Arthritis Research & Therapy, 2014
    Co-Authors: Congming Zhang, Yongping Li, Shaowei Wang, Pengcui Li
    Abstract:

    Introduction To investigate if decreased histone deacetylase 4 (HDAC4) is associated with human osteoarthritis (OA) Cartilage Degeneration by releasing HDAC4 inhibition of runt-related transcription factor-2 (Runx2) resulting in increase of OA Cartilage Degeneration-related genes.

  • decreased histone deacetylase 4 is associated with human osteoarthritis Cartilage Degeneration by releasing histone deacetylase 4 inhibition of runt related transcription factor 2 and increasing osteoarthritis related genes a novel mechanism of human
    Arthritis Research & Therapy, 2014
    Co-Authors: Kun Cao, Congming Zhang, Shaowei Wang, Lei Wei, Zhiqiang Zhang, Li Guo, Changqi Sun, Xiaojuan Sun, Xiaochun Wei
    Abstract:

    To investigate if decreased histone deacetylase 4 (HDAC4) is associated with human osteoarthritis (OA) Cartilage Degeneration by releasing HDAC4 inhibition of runt-related transcription factor-2 (Runx2) resulting in increase of OA Cartilage Degeneration-related genes. The mRNA and protein levels of HDAC4, Runx2, matrix metalloproteinase (MMP)-13, Indian hedgehog (Ihh) and type X collagen were detected by performing real-time PCR (RT-PCR), western blotting and immunohistochemistry on specimens from human OA and normal Cartilage. To further explore the mechanism of regulation of Runx2 and OA-related genes by HDAC4, changes in these OA-related genes were further quantified by RT-PCR after overexpression of HDAC4 and knockdown of HDAC4 by siRNA. Runx2 and MMP-13 promoter activities were measured by dual luciferase assays. The levels of HDAC4 in the Cartilage from OA patients and healthy 40- to 60-year-old donors were decreased to 31% and 65% compared with specimens from 20- to 40-year-old healthy donors, respectively (P <0.05). Decreased HDAC4 was associated with increased Runx2 and other OA-related genes in human OA Cartilage, specifically: MMP-13, Ihh and type X collagen. Exogenous HDAC4 decreased the mRNA levels of Runx2, MMP1, MMP3, MMP-13, type X collagen, Ihh, ADAMTS-4 and -5, and increased the mRNA of type II collagen. In addition, the data also shows that overexpression of HDAC4 not only decreased the expression of interleukin (IL)-1β, Cox2 and iNos and increased the expression of aggrecan, but also partially blocked the effect of IL-1β on expression of catabolic events in human OA chondrocytes. HDAC4 also inhibited Runx2 promoter activity and MMP13 promotor activity in a dose-dependent manner. In contrast, inhibition of HDAC4 by TSA drug had an opposite effect. Our study is the first to demonstrate that decreased HDAC4 contributes, at least in part, to the pathogenesis of OA Cartilage Degeneration. Thus, HDAC4 may have chondroprotective properties by inhibiting Runx2 and OA-related genes.