SP0013 GROWTH FACTORS AND CARTILAGE: FROM MECHANISMS TO DMOADS

Background: Growth factors are biologically active molecules that can stimulate cellular division, growth and differentiation and, in articular cartilage, can regulate development, homeostasis and regeneration of matrix. These anabolic factors can stimulate synthesis of proteoglycans, aggrecan and type II collagen, induce mesenchymal stem cell (MSC) proliferation and drive differentiation of MSCs into chondrocytes and decrease catabolic effects of cytokines and matrix metalloproteinases (MMPs). Growth factors would not, however, be expected to have a direct analgesic effect in patients with symptomatic knee osteoarthritis. Objectives: To review the role of growth factors in articular cartilage, identify specific growth factors and review data from phase 1 and 2 studies of selected growth factors in subjects with knee osteoarthritis. Methods: A PubMed search was performed using key words “cartilage or chondrocyte” and “growth factor”. The search included both original manuscripts and review articles as well as clinical trials but was limited to English language. From these searches, I selected review articles and clinical trials and excluded articles that solely examined molecular mechanisms of action of growth factors on chondrocytes. Results: Growth factors for articular cartilage include molecules in the transforming growth factor-β (TGF-ββ superfamily (including TGF-β1, bone morphogenic protein [BMP]-2 and BMP-7), insulin-like growth factor-I, fibroblast growth factor (FGF) family (including FGF-2 and FGF-18), platelet-derived growth factor (PDGF) and Wnt ligands as well as platelet rich plasma (PRP). Conclusion: Data will be presented from phase 1 and 2 studies of rhFGF-18 and SM-04690, a Wnt signaling inhibitor, that demonstrate proof-of-concept and early efficacy of these growth factors for structure modifying effects in subjects with knee osteoarthritis (OA). References: [1] Boehme KA, Rolauffs B: Onset and progression of human osteoarthritis - can growth factors, inflammatory cytokines, or differential miRNA expression concomitantly induce proliferation, ECM degradation, and inflammation in articular cartilage? Int J Mol Sci 2018;19:2282;doi:10.3390/ijms19082282. [2] Zhu Z, Li J, Ruan G, Wang G, Huang C, Ding C: Investigational drugs for the treatment of osteoarthritis, an update on recent developments. Expert Opin Invest Drugs 2018. doi.org/10.1080/13543784.2018.1539075. Disclosure of Interests: Marc Hochberg Shareholder of: BriOri Biotech, Theralogix LLC., Consultant for: Bristol Myers Squibb, Eli Lilly, EMD Serono, Novartis Pharma AG, Pfizer Inc., Samumed LLC, Symic Bio Inc., Theralogix LLC, TissueGene Inc., TLC Biopharmaceuticals, Inc., Zynerba, Galapagos, IQVIA, Hoffman LaRoche.