The Experts below are selected from a list of 1539 Experts worldwide ranked by ideXlab platform
Andrew D Rowan - One of the best experts on this subject based on the ideXlab platform.
-
proteinase activated receptor 2 modulates oa related pain cartilage and bone pathology
Annals of the Rheumatic Diseases, 2016Co-Authors: C Huesa, Ana C Ortiz, L Dunning, Laura Mcgavin, Louise Bennett, Kathryn Mcintosh, A Crilly, Mariola Kurowskastolarska, Robin Plevin, Andrew D RowanAbstract:Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2 −/− ) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2 −/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but Osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2 −/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no Osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2 −/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2 −/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, Osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes.
Gaetano Bulfamante - One of the best experts on this subject based on the ideXlab platform.
-
prognostic significance of a comprehensive histological evaluation of reticulin fibrosis collagen deposition and Osteosclerosis in primary myelofibrosis patients
Histopathology, 2017Co-Authors: Umberto Gianelli, Stefano Fiori, Ivan Cortinovis, Arturo Bonometti, Giulia Ercoli, Alberto Bossi, Daniele Cattaneo, Nicola Orofino, Cristina Bucelli, Gaetano BulfamanteAbstract:Aims to evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. Methods reticulin fibrosis, collagen deposition and Osteosclerosis were graded from 0 to 3 in a series of 122 base-line BMBs. Then, we assigned to each case a comprehensive score (RCO score, ranging from 0 to 9) that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Results and discussion of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was more frequently associated with anemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. RCO score resulted strictly correlated with overall mortality (p=0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (Log-Rank test: p<0.001). Moreover, it proved to be more accurate than the European Consensus on grading of bone marrow fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. Conclusion the comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis, resulted prognostically significant, more accurate than ECGMF grade in identifying high-risk patients, and improved PPV when applied in addition to IPSS. This article is protected by copyright. All rights reserved.
-
prognostic significance of a comprehensive histological evaluation of reticulin fibrosis collagen deposition and Osteosclerosis in primary myelofibrosis patients
Histopathology, 2017Co-Authors: Umberto Gianelli, Stefano Fiori, Ivan Cortinovis, Arturo Bonometti, Giulia Ercoli, Alberto Bossi, Daniele Cattaneo, Nicola Orofino, Cristina Bucelli, Gaetano BulfamanteAbstract:Aims to evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. Methods reticulin fibrosis, collagen deposition and Osteosclerosis were graded from 0 to 3 in a series of 122 base-line BMBs. Then, we assigned to each case a comprehensive score (RCO score, ranging from 0 to 9) that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Results and discussion of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was more frequently associated with anemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. RCO score resulted strictly correlated with overall mortality (p=0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (Log-Rank test: p<0.001). Moreover, it proved to be more accurate than the European Consensus on grading of bone marrow fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. Conclusion the comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis, resulted prognostically significant, more accurate than ECGMF grade in identifying high-risk patients, and improved PPV when applied in addition to IPSS. This article is protected by copyright. All rights reserved.
-
Prognostic significance of a comprehensive histologic evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in primary myelofibrosis patients.
'Wiley', 2017Co-Authors: Umberto Gianelli, Stefano Fiori, Ivan Cortinovis, Arturo Bonometti, Giulia Ercoli, Alberto Bossi, Daniele Cattaneo, Nicola Orofino, Cristina Bucelli, Gaetano BulfamanteAbstract:AimsTo evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. Methods and resultsReticulin fibrosis, collagen deposition and Osteosclerosis were graded from 0 to 3 in a series of 122 baseline BMBs. Then, we assigned to each case a comprehensive score [reticulin, collagen, Osteosclerosis (RCO) score, ranging from 0 to 9] that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was associated more frequently with anaemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. The RCO score was correlated strictly with overall mortality (P = 0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (log-rank test: P < 0.001). Moreover, it proved to be more accurate than the European Consensus on Grading of Bone Marrow Fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. ConclusionThe comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis was prognostically significant and more accurate than ECGMF grade in identifying high-risk patients and improved PPV when applied in addition to IPSS
C Huesa - One of the best experts on this subject based on the ideXlab platform.
-
proteinase activated receptor 2 modulates oa related pain cartilage and bone pathology
Annals of the Rheumatic Diseases, 2016Co-Authors: C Huesa, Ana C Ortiz, L Dunning, Laura Mcgavin, Louise Bennett, Kathryn Mcintosh, A Crilly, Mariola Kurowskastolarska, Robin Plevin, Andrew D RowanAbstract:Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2 −/− ) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2 −/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but Osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2 −/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no Osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2 −/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2 −/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, Osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes.
Umberto Gianelli - One of the best experts on this subject based on the ideXlab platform.
-
prognostic significance of a comprehensive histological evaluation of reticulin fibrosis collagen deposition and Osteosclerosis in primary myelofibrosis patients
Histopathology, 2017Co-Authors: Umberto Gianelli, Stefano Fiori, Ivan Cortinovis, Arturo Bonometti, Giulia Ercoli, Alberto Bossi, Daniele Cattaneo, Nicola Orofino, Cristina Bucelli, Gaetano BulfamanteAbstract:Aims to evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. Methods reticulin fibrosis, collagen deposition and Osteosclerosis were graded from 0 to 3 in a series of 122 base-line BMBs. Then, we assigned to each case a comprehensive score (RCO score, ranging from 0 to 9) that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Results and discussion of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was more frequently associated with anemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. RCO score resulted strictly correlated with overall mortality (p=0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (Log-Rank test: p<0.001). Moreover, it proved to be more accurate than the European Consensus on grading of bone marrow fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. Conclusion the comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis, resulted prognostically significant, more accurate than ECGMF grade in identifying high-risk patients, and improved PPV when applied in addition to IPSS. This article is protected by copyright. All rights reserved.
-
prognostic significance of a comprehensive histological evaluation of reticulin fibrosis collagen deposition and Osteosclerosis in primary myelofibrosis patients
Histopathology, 2017Co-Authors: Umberto Gianelli, Stefano Fiori, Ivan Cortinovis, Arturo Bonometti, Giulia Ercoli, Alberto Bossi, Daniele Cattaneo, Nicola Orofino, Cristina Bucelli, Gaetano BulfamanteAbstract:Aims to evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. Methods reticulin fibrosis, collagen deposition and Osteosclerosis were graded from 0 to 3 in a series of 122 base-line BMBs. Then, we assigned to each case a comprehensive score (RCO score, ranging from 0 to 9) that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Results and discussion of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was more frequently associated with anemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. RCO score resulted strictly correlated with overall mortality (p=0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (Log-Rank test: p<0.001). Moreover, it proved to be more accurate than the European Consensus on grading of bone marrow fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. Conclusion the comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis, resulted prognostically significant, more accurate than ECGMF grade in identifying high-risk patients, and improved PPV when applied in addition to IPSS. This article is protected by copyright. All rights reserved.
-
Prognostic significance of a comprehensive histologic evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in primary myelofibrosis patients.
'Wiley', 2017Co-Authors: Umberto Gianelli, Stefano Fiori, Ivan Cortinovis, Arturo Bonometti, Giulia Ercoli, Alberto Bossi, Daniele Cattaneo, Nicola Orofino, Cristina Bucelli, Gaetano BulfamanteAbstract:AimsTo evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications. Methods and resultsReticulin fibrosis, collagen deposition and Osteosclerosis were graded from 0 to 3 in a series of 122 baseline BMBs. Then, we assigned to each case a comprehensive score [reticulin, collagen, Osteosclerosis (RCO) score, ranging from 0 to 9] that allowed us to distinguish two groups of patients, with low-grade (RCO score 0-4) and high-grade (RCO score 5-9) stromal changes. Of 122 patients, 88 displayed a low-grade and 34 a high-grade RCO score. The latter was associated more frequently with anaemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. The RCO score was correlated strictly with overall mortality (P = 0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low- and high-grade patients (log-rank test: P < 0.001). Moreover, it proved to be more accurate than the European Consensus on Grading of Bone Marrow Fibrosis (ECGMF grade) in identifying high-risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical-pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high-risk patients. ConclusionThe comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and Osteosclerosis was prognostically significant and more accurate than ECGMF grade in identifying high-risk patients and improved PPV when applied in addition to IPSS
Laura Mcgavin - One of the best experts on this subject based on the ideXlab platform.
-
proteinase activated receptor 2 modulates oa related pain cartilage and bone pathology
Annals of the Rheumatic Diseases, 2016Co-Authors: C Huesa, Ana C Ortiz, L Dunning, Laura Mcgavin, Louise Bennett, Kathryn Mcintosh, A Crilly, Mariola Kurowskastolarska, Robin Plevin, Andrew D RowanAbstract:Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2 −/− ) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2 −/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but Osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2 −/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no Osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2 −/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2 −/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, Osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes.
