The calcitonin receptor controls osteophyte formation, but not cartilage degeneration and subchondral bone loss in experimental osteoarthritis

Aims Salmon calcitonin (CT) has been shown to have antiresorptive and chondroprotective efects, and several clinical trials have reported benefcial efects of salmon CT treatment in patients with knee osteoarthritis (OA). The objective of the present study is to investigate the role of endogenous CT-mediated signalling in OA. Methods Calcitonin receptor (CTR)-defcient mice and wild-type (WT) littermate controls were subjected to experimental post-traumatic OA (ptOA) by anterior cruciate ligament transection (ACLT). Radiological and histomorphometric outcome measurements in WT and CTR-defcient mice with ACLT were performed at early (4 weeks) and late (8 weeks) stages after ptOA induction. Expression of CTR on messenger RNA (mRNA) and protein level in sham and ACLT knees of WT mice were measured by gene expression analysis and immuno-fuorescence, respectively. Results In WT mice, Calcr mRNA was progressively induced in ptOA knees, and CTR protein was abundantly expressed in articular cartilage and subchondral bone (SB) in diseased joints. CTR^-/- mice displayed decreased osteophyte formation compared to WT mice, while cartilage deterioration, pathological SB alterations, and synovial infammation were not afected by CTR defciency. In line with this, bone resorption, cartilage, and infammatory markers were unaltered between WT and CTR-defcient mice, while bone formation parameters were increased only in WT ptOA knees on gene expression level four weeks after surgery. Conclusion Although CTR is highly expressed in articular cartilage and SB and promotes osteophyte formation, endogenous CTR signalling does not afect cartilage degeneration and SB pathologies in murine ptOA.