期刊
BIOMATERIALS
卷 180, 期 -, 页码 91-103出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.07.011
关键词
Squid type II collagen; M2 macrophage; Immunomodulation; Cartilage repair; Apoptosis; Chondrocyte hypertrophy
资金
- National Natural Science Foundation of China [31470917]
- Shanghai Sci-Tech Committee Foundation-Pujiang Program [18PJD024]
- National Key Research and Development Program of China [SQ2018YFC110129]
Cartilage lesions in degenerative osteoarthritis (OA) are involved with pathological microenvironmental alterations induced by inflammatory macrophages, and apoptotic and/or hypertrophic chondrocytes. However, current non-operative therapies for cartilage repair in OA can rarely achieve long-term and satisfactory outcomes. This study aims to evaluate a newly developed squid type II collagen (SCII) for repairing OA-induced cartilage lesions. Our in vitro data show that SCII induces M2 polarization of macrophages, and activates macrophages to express pro-chondrogenic genes (TGF-beta and IGF), which greatly improves the microenvironment around chondrocytes to produce type II collagen and glycosaminoglycan. In addition, glycine in SCII activates glycine receptors on inflammatory chondrocytes to decrease intracellular calcium concentration, leading to effective inhibition of chondrocyte apoptosis and hypertrophy. The in vitro effects of SCII are further confirmed in vivo. In a rat model of OA, SCII increases the ratio of M2 macrophages, elevates the levels of pro-chondrogenic cytokines (TGF-beta 1 and TGF-beta 3) in synovial fluid, and inhibits chondrocyte apoptosis and MMP13 production. Our findings show that SCII immunomodulates M2 activation of macrophages to skew the local OA microenvironment towards a prochondrogenic atmosphere, and promotes cartilage repair under inflammatory condition. It shows great potential for SCII to be a novel biomaterial for cartilage repair in OA. (C) 2018 Elsevier Ltd. All rights reserved.
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