Novel Mechanism and Treatment for Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease associated with pain. However, clinical evidence demonstrated that joint structure damage and OA pain may not always be consistent. The phenonmenon of separation of joint structure damage and OA pain was observed in some OA patients. To determine the role and underlying mechanisms of calcitonin gene related peptide (CGRP) in OA progression and in OA pain. We generated knockout mice with deletion of both CGRP-α and CGRP-β genes. We analyzed changes in joint structure and did not observe significant changes in articular cartilage, subchondral bone and osteophyte formation without or with destabilization of medial meniscus (DMM) surgery by histology, immunohistochemistry (IHC) and micro-CT analyses. In contrast, the results of von Frey test (examining mechanical allodynia), hot plate test (examining thermal allodynia) and LABORAS system (examining spontaneous activity) showed that deletion of CGRP-α and CGRP-β genes significantly relieves DMM-induced pain, suggesting that CGRP inhibition has protective effect on OA pain. Immunofluorescence (IF) staining of expression of neural markers in joint tissues and in dorsal root ganglion (DRG) reveals consistent results. Similarly clinical studies also showed dissociation of joint damage and OA pain. Our studies indicate that CGRP has differential effects on joint damage and OA pain and provide significant insights into OA treatment.