Increased synovial expression of calcitonin gene-related peptide and its potential roles in Charcot Neuroarthropathy

Objective: Joint destruction in Charcot neuroarthropathy (CNA) is accompanied with abundant hyperplastic synovium. This study aimed to characterize the expression patterns of a group of neuropeptides in the CNA synovium. Methods: Synovial specimens were collected during surgery from the CNA (n = 6) and non-CNA joints (n = 14). Tissue samples were processed for protein extraction and western blot for vasoactive intestinal peptide (VIP), galanin, and calcitonin gene-related peptide (CGRP). Immunohistochemistry was performed to localize CGRP in the CNA synovium. Additionally, CGRP was applied to fibroblast-like synoviocytes (FLS) isolated from CNA synovium for its effects on cell proliferation and collagenolysis in vitro. Results: Western blot detected light bands of VIP in the CNA samples but abundant galanin in both CNA and non-CNA samples. Most of the CNA samples (5/6) increased expression of CGRP, with an average band density about 2 times that in the non-CNA group (p <.05). Immunohistochemistry of CGRP demonstrated intense staining in the intimal layer of the CNA synovium. In tissue culture, adding CGRP (10 nM) in the medium promoted FLS proliferation. In combination with TNF-α, CGRP enhanced FLS-mediated collagenolysis in vitro. Conclusion: This study revealed an increased expression of CGRP in the CNA synovium and demonstrated that CGRP regulates FLS proliferation and collagenolytic activity, suggesting CGRP may contribute to the bone and cartilage destruction in CNA.