D D Chan1, W F Xiao2, J Li3, C A de la Motte4, J D Sandy5, A Plaas6. 1. Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. Electronic address: deva_chan@rush.edu. 2. Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: wenfeng_xiao@163.com. 3. Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. Electronic address: jun_li@rush.edu. 4. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: delamoc@ccf.org. 5. Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA. Electronic address: jsandy44@gmail.com. 6. Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA; Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA. Electronic address: anna_plaas@rush.edu.
Abstract
OBJECTIVE: Articular cartilage defects commonly result from traumatic injury and predispose to degenerative joint diseases. To test the hypothesis that aberrant healing responses and chronic inflammation lead to osteoarthritis (OA), we examined spatiotemporal changes in joint tissues after cartilage injury in murine knees. Since intra-articular injection of hyaluronan (HA) can attenuate injury-induced osteoarthritis in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1(-/-)). DESIGN: Femoral groove cartilage of WT and Has1(-/-) mice was debrided to generate a non-bleeding wound. Macroscopic imaging, histology, and gene expression were used to evaluate naïve, sham-operated, and injured joints. RESULTS: Acute responses (1-2 weeks) in injured joints from WT mice included synovial hyperplasia with HA deposition and joint-wide increases in expression of genes associated with inflammation, fibrosis, and extracellular matrix (ECM) production. By 4 weeks, some resurfacing of damaged cartilage occurred, and early cell responses were normalized. Cartilage damage in Has1(-/-) mice also induced early responses; however, at 4 weeks, inflammation and fibrosis genes remained elevated with widespread cartilage degeneration and fibrotic scarring in the synovium and joint capsule. CONCLUSIONS: We conclude that the ineffective repair of injured cartilage in Has1(-/-) joints can be at least partly explained by the markedly enhanced expression of particular genes in pathways linked to ECM turnover, IL-17/IL-6 cytokine signaling, and apoptosis. Notably, Has1 ablation does not alter gross HA content in the ECM, suggesting that HAS1 has a unique function in the metabolism of inflammatory HA matrices.
OBJECTIVE:Articular cartilage defects commonly result from traumatic injury and predispose to degenerative joint diseases. To test the hypothesis that aberrant healing responses and chronic inflammation lead to osteoarthritis (OA), we examined spatiotemporal changes in joint tissues after cartilage injury in murine knees. Since intra-articular injection of hyaluronan (HA) can attenuate injury-induced osteoarthritis in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1(-/-)). DESIGN:Femoral groove cartilage of WT and Has1(-/-) mice was debrided to generate a non-bleeding wound. Macroscopic imaging, histology, and gene expression were used to evaluate naïve, sham-operated, and injured joints. RESULTS: Acute responses (1-2 weeks) in injured joints from WT mice included synovial hyperplasia with HA deposition and joint-wide increases in expression of genes associated with inflammation, fibrosis, and extracellular matrix (ECM) production. By 4 weeks, some resurfacing of damaged cartilage occurred, and early cell responses were normalized. Cartilage damage in Has1(-/-) mice also induced early responses; however, at 4 weeks, inflammation and fibrosis genes remained elevated with widespread cartilage degeneration and fibrotic scarring in the synovium and joint capsule. CONCLUSIONS: We conclude that the ineffective repair of injured cartilage in Has1(-/-) joints can be at least partly explained by the markedly enhanced expression of particular genes in pathways linked to ECM turnover, IL-17/IL-6 cytokine signaling, and apoptosis. Notably, Has1 ablation does not alter gross HA content in the ECM, suggesting that HAS1 has a unique function in the metabolism of inflammatory HA matrices.
Authors: Teun Teunis; Michiel Beekhuizen; Gerjo V M Van Osch; Arnold H Schuurman; Laura B Creemers; L Paul van Minnen Journal: Arch Bone Jt Surg Date: 2014-09-15
Authors: D F G Remst; A B Blom; E L Vitters; R A Bank; W B van den Berg; E N Blaney Davidson; P M van der Kraan Journal: Arthritis Rheumatol Date: 2014-03 Impact factor: 10.995
Authors: Carol A de la Motte; Vincent C Hascall; Judith Drazba; Sudip K Bandyopadhyay; Scott A Strong Journal: Am J Pathol Date: 2003-07 Impact factor: 4.307
Authors: Y Xu; M J Barter; D C Swan; K S Rankin; A D Rowan; M Santibanez-Koref; J Loughlin; D A Young Journal: Osteoarthritis Cartilage Date: 2012-05-31 Impact factor: 6.576
Authors: Meghan M Moran; Brittany M Wilson; Jun Li; Phillip A Engen; Ankur Naqib; Stefan J Green; Amarjit S Virdi; Anna Plaas; Christopher B Forsyth; Ali Keshavarzian; Dale R Sumner Journal: FASEB J Date: 2020-09-15 Impact factor: 5.191
Authors: Katie J Sikes; Kristen Renner; Jun Li; K Jane Grande-Allen; Jennifer P Connell; Valbona Cali; Ronald J Midura; John D Sandy; Anna Plaas; Vincent M Wang Journal: J Orthop Res Date: 2018-07-13 Impact factor: 3.494
Authors: Kyle Jones; Marco Angelozzi; Umesh Gangishetti; Abdul Haseeb; Charles de Charleroy; Véronique Lefebvre; Pallavi Bhattaram Journal: ACR Open Rheumatol Date: 2021-05-01