The Protective Effects of Parathyroid Hormone (1‐34) on Cartilage and Subchondral Bone Through Down‐Regulating JAK2/STAT3 and WNT5A/ROR2 in a Collagenase‐Induced Osteoarthritis Mouse Model

Abstract

Objective To assess the effects of PTH (1‐34) on bone and cartilage metabolism in a collagenase‐induced mouse model of osteoarthritis (OA) and examine whether PTH (1‐34) affects the expression of JAK2/STAT3 and WNT5A/ROR2 in this process. Methods Eighteen 12‐week‐old male C57Bl/6 mice were randomly assigned into three groups as follows: sham group (Group A), the collagenase + saline injection group (Group B), and the collagenase + PTH (1‐34) treatment group (Group C). Collagenase was injected (intra‐articular) into the knee joint of Group B and C. The PTH (1–34)‐treatment was started at 6 weeks after the operation and lasted for 6 weeks. Cartilage pathology was evaluated by gross visual, histological, and immunohistochemical assessments. Subchondral bone was evaluated by microcomputed tomography (micro‐CT) and immunohistochemical analyses. Results The OARSI macroscopic and microscopic scores of Group B were higher than those of Group A (P = 0.026; P = 0.002, respectively). Group C showed statistically significant differences in macroscopic and microscopic scores from Group B (P = 0.041; P = 0.008, respectively). The results showed that the Col‐II and AGG expression levels in the cartilage tissue were significantly lower in Group B than Group A (P < 0.001; P = 0.008, respectively). The Col‐II and AGG expression levels were significantly higher in Group C than Group B (P = 0.009; P = 0.014, respectively). MMP‐13, ADAMTS‐4, Caspase‐3, P53, and Bax expression levels were significantly higher in Group B than the Group A (P < 0.001; P < 0.001; P = 0.04; P < 0.001; P = 0.005, respectively); however, the cartilage tissue in Group C showed significantly less ADAMTS‐4, MMP‐13, Caspase‐3, P53, and Bax expression than Group B (P < 0.001, P < 0.001, P = 0.044; P = 0.002; P = 0.005, respectively). Over‐expressed JAK2/STAT3 and WNT5A/ROR2 were observed in both cartilage and subchondral bone in this model; however, these changes were prevented by PTH (1‐34) treatment. These parameters (bone mineral density, bone volume ratio, trabecular bone pattern factor, and structure model index) of micro‐CT indicated subchondral bone loss and architecture changes in Group B, but improvements in these parameters in Group C. Conclusions PTH (1‐34) exhibits protective effects on both cartilage and subchondral bone in a collagenase‐induced OA mouse model, and it may be involved in down‐regulating the expression of JAK2/STAT3 and WNT5A/ROR2.

Keywords

• Cartilage
• JAK2
• Osteoarthritis
• Parathyroid hormone
• Subchondral bone