S Zaki1, M M Smith2, S M Smith3, C B Little4. 1. Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Australia; Raymond Purves Bone and Joint Laboratory, Kolling Institute, Institute of Bone and Joint Research, University of Sydney Faculty of Medicine and Health, at Royal North Shore Hospital, Australia. Electronic address: sanaa.zaki@sydney.edu.au. 2. Raymond Purves Bone and Joint Laboratory, Kolling Institute, Institute of Bone and Joint Research, University of Sydney Faculty of Medicine and Health, at Royal North Shore Hospital, Australia. Electronic address: mobsmith@sydney.edu.au. 3. Raymond Purves Bone and Joint Laboratory, Kolling Institute, Institute of Bone and Joint Research, University of Sydney Faculty of Medicine and Health, at Royal North Shore Hospital, Australia. Electronic address: susan.smith@sydney.edu.au. 4. Raymond Purves Bone and Joint Laboratory, Kolling Institute, Institute of Bone and Joint Research, University of Sydney Faculty of Medicine and Health, at Royal North Shore Hospital, Australia. Electronic address: christopher.little@sydney.edu.au.
Abstract
OBJECTIVE: To determine if osteoarthritis (OA) progression and joint tissue-pathology associations link specific animal models to different human OA phenotypes. DESIGN: Male 11-week-old C57BL6 mice had unilateral medial-meniscal-destabilization (DMM) or antigen-induced-arthritis (AIA). Joint tissue histopathology was scored day-3 to week-16. Tissue-pathology associations (corrected for time and at week-16) were determined by partial correlation coefficients, and odds ratios (OR) calculated for likelihood of cartilage damage and joint inflammation by ordinal-logistic-regression. RESULTS: Despite distinct temporal patterns of progression, by week-16 joint-wide OA pathology in DMM and AIA was equivalent. Significant pathology associations common to both models included: osteophyte size and maturity (r > 0.4); subchondral bone (SCB) sclerosis and osteophyte maturity (r > 0.25); cartilage erosion and chondrocyte hypertrophy/apoptosis (r > 0.4), SCB sclerosis (r > 0.26), osteophyte size (r > 0.3), and maturity (r > 0.32). DMM-specific associations were between cartilage proteoglycan loss and structural damage (r = 0.56), osteophyte maturity (r = 0.49), size (r = 0.45), and SCB sclerosis (r = 0.28). AIA-specific associations were between SCB sclerosis and chondrocyte hypertrophy/apoptosis (r = 0.40) and osteophyte size (r = 0.37); and synovitis with cartilage structural damage (r = 0.18). No tissue-pathology associations were common to both models at week-16. Increased likelihood of cartilage structural damage was associated with: chondrocyte hypertrophy/apoptosis (OR>1.7), and osteophyte size (OR>2.3) in both models; SCB sclerosis (OR = 2.0) and proteoglycan loss (OR = 2.4) in DMM; and synovitis (OR = 1.2) in AIA. Joint inflammation was associated positively with cartilage proteoglycan loss (OR = 1.4) and inversely with osteophyte size (OR = 0.21) in AIA only. CONCLUSION: This study highlights the importance of defining OA-models by initiating mechanisms and progression, not just end-stage joint-tissue pathology.
OBJECTIVE: To determine if osteoarthritis (OA) progression and joint tissue-pathology associations link specific animal models to different human OA phenotypes. DESIGN: Male 11-week-old C57BL6 mice had unilateral medial-meniscal-destabilization (DMM) or antigen-induced-arthritis (AIA). Joint tissue histopathology was scored day-3 to week-16. Tissue-pathology associations (corrected for time and at week-16) were determined by partial correlation coefficients, and odds ratios (OR) calculated for likelihood of cartilage damage and joint inflammation by ordinal-logistic-regression. RESULTS: Despite distinct temporal patterns of progression, by week-16 joint-wide OA pathology in DMM and AIA was equivalent. Significant pathology associations common to both models included: osteophyte size and maturity (r > 0.4); subchondral bone (SCB) sclerosis and osteophyte maturity (r > 0.25); cartilage erosion and chondrocyte hypertrophy/apoptosis (r > 0.4), SCB sclerosis (r > 0.26), osteophyte size (r > 0.3), and maturity (r > 0.32). DMM-specific associations were between cartilage proteoglycan loss and structural damage (r = 0.56), osteophyte maturity (r = 0.49), size (r = 0.45), and SCB sclerosis (r = 0.28). AIA-specific associations were between SCB sclerosis and chondrocyte hypertrophy/apoptosis (r = 0.40) and osteophyte size (r = 0.37); and synovitis with cartilage structural damage (r = 0.18). No tissue-pathology associations were common to both models at week-16. Increased likelihood of cartilage structural damage was associated with: chondrocyte hypertrophy/apoptosis (OR>1.7), and osteophyte size (OR>2.3) in both models; SCB sclerosis (OR = 2.0) and proteoglycan loss (OR = 2.4) in DMM; and synovitis (OR = 1.2) in AIA. Joint inflammation was associated positively with cartilage proteoglycan loss (OR = 1.4) and inversely with osteophyte size (OR = 0.21) in AIA only. CONCLUSION: This study highlights the importance of defining OA-models by initiating mechanisms and progression, not just end-stage joint-tissue pathology.
Authors: Andrew Bowen; David Shamritsky; Josue Santana; Ian Porter; Erica Feldman; Sarah L Pownder; Matthew F Koff; Kei Hayashi; Christopher J Hernandez Journal: JBMR Plus Date: 2022-02-15