Squid cartilage type II collagen accelerates osteoporotic fractures healing through regulating homocysteine mediated EGF and FBN1 signals

Abstract

Osteoporosis fracture (OPF) is a serious social public health concern in humans. Type II collagen from squid cartilage (SCII) has been proven to promote the healing process in normal fracture mice, however, the effect and mechanism of SCII to improve osteoporosis fracture remain unknown. In this study, type II collagen was obtained from squid laryngeal cartilage, and the effects of SCII on OPF were investigated in mice that experienced bilateral ovariectomy and open tibial fracture surgery after oral administration. The results showed that SCII supplementation significantly decreased the serum TNF-α, increased aggrecan levels on the 5 d, and elevated the serum TGF-β and Col10α levels on 13 d after fracture. Notably, H&E staining exhibited an obvious chondrocyte proliferation on 5 d, and a specific promotion of chondrocyte hypertrophic differentiation and mineralization in the SCII group on 13 d. These findings suggested that SCII promoted osteoporosis fracture healing by enhancing the proliferation and hypertrophy of chondrocyte. Mechanically, SCII supplementation significantly reduced homocysteine levels through down-regulating TMAO production and bile acid levels and activated the EGF/AKT/CylinD1 and TGFβ/Smad1/5/8 pathways, thereby recovering the delay of chondrocyte proliferation and hypertrophy in OPF mice. This study investigated the effects of SCII on osteoporosis fracture healing for the first time and provided a new theoretical basis and options for the high-value application of squid cartilage.