Abstract # 2078 Norepinephrine (NE) inhibits chondrogenic differentiation of synovial adipose-derived stem cells (ASCs)

Sympathetic nerve fibers and NE are present in healthy and osteoarthritic (OA) synovial tissue and fluid. The potential regenerative role of progenitors in cartilage has been confirmed, though, in OA, these cells exhibit reduced chondrogenic capacity. The aim of this study was to explore the role of NE on proliferation and chondrogenesis of ASCs. Synovium was obtained from OA patients undergoing total knee replacement. For proliferation and chondrogenesis experiments, cells were treated with NE (10–9 – 10–6 M) or specific alpha- and beta-adrenergic receptor (AR) agonists under physioxia (2% O2). Cell number, viability, AR profile, pellet size, sulfated glycosaminoglycan (sGAG) deposition, type II collagen synthesis, hypertrophic marker gene expression, and dsDNA content was analyzed. ASCs expressed alpha1b, alpha2a, alpha2b, alpha2c, and beta2AR. NE or specific agonists had no significant effect on proliferation. Chondrogenic pellets expressed alpha1b, alpha2a, alpha2b, alpha2c, and beta2AR. Pellets treated with 10–7 or 10–6 M NE or with specific beta2AR agonist were significantly smaller compared to untreated controls, while dsDNA was constant. NE in high concentrations or the beta2AR agonist decreased sGAG and type II collagen content. No differences were observed on hypertrophic genes (MMP13, Runx2). Our study confirms the important role of NE in progenitor cell chondrogenic function and new insights in OA pathophysiology. Future studies might unravel the potential of novel neuroendocrine-chondrogenic therapeutic options for OA treatment.