Because cartilage lacks nerves, blood vessels, and lymphatic vessels, it is thought to contain factors that inhibit the growth and development of those tissues. Chondroitin sulfate proteoglycans (CSPGs) are a major extracellular component in cartilage. CSPGs contribute to joint flexibility and regulate extracellular signaling via their attached glycosaminoglycan, chondroitin sulfate (CS). CS and CSPG inhibit axonal regeneration; however, their role in blood vessel formation is largely unknown. To clarify the function of CSPG in blood vessel formation, we tested salmon nasal cartilage proteoglycan (PG), a member of the aggrecan family of CSPG, for endothelial capillary-like tube formation. Treatment with salmon PG inhibited endothelial cell adhesion and in vitro tube formation. The anti-angiogenic activity was derived from CS in the salmon PG but not the core protein. Salmon PG also reduced matrix metalloproteinase expression and inhibited angiogenesis in the chick chorioallantoic membrane. All of these data support an anti-angiogenic role for CSPG in cartilage.
Keywords: Aggrecan; Angiogenesis; BME, basement membrane extract; BSA, bovine serum albumin; CAM, chorioallantoic membrane; CS, chondroitin sulfate; CSPG, chondroitin sulfate proteoglycan; Chondroitin sulfate proteoglycan; ECM, extracellular matrix; FAK, focal adhesion kinase; FBS, fetal bovine serum; GAG, glycosaminoglycan; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GalNAc, N-acetylgalactosamine; GdnHCl, guanidine hydrochloride; GlcUA, glucuronic acid; Glycosaminoglycan; HSPG, heparan sulfate proteoglycan; KSPG, keratin sulfate proteoglycan; MMP, matrix metalloproteinase; Matrix metalloproteinase; OA, osteoarthritis; PBS, phosphate-buffered saline; PG, proteoglycan; UA, uronic acid; Vascular endothelial cell.