Biocompatible and bioactive yak bone collagen hydrolysates with controllable molecular weight for effective prevention of osteoporosis

Osteoporosis is a prevalent systemic disease characterized by the change of bone structure and function, significantly affecting the human health. Oral collagen hydrolysates have garnered increasing attention for the prevention and treatment of osteoporosis due to their advantages of low molecular weight, easy absorption, and high biological activity; however, they suffer from severe concerns including uncontrollable molecular weights, limited biocompatibility, and unclear correlations between molecular weight and efficacy. Herein, we have for the first time developed a series of yak bone collagen hydrolysates (YBCH) with controllable molecular weight for effective prevention of osteoporosis. The YBCH exhibited low (LYBCH, M < 1000 Da), medium (MYBCH, 1000 < M < 3000 Da), high (HYBCH, 3000 < M < 10000 Da), and ultra-high (UYBCH, M > 10000 Da) molecular weight, respectively. An osteoporosis mouse model was established to evaluate the therapeutic effects of YBCH. Histological analysis indicated that YBCH could ameliorate pathological changes of osteoporosis by increasing bone mass and promoting collagen regeneration, with MYBCH showing the most pronounced effect. Micro-CT results revealed that MYBCH significantly enhanced the microstructure of osteoporotic bone by increasing BMD, BV/TV, Tb.N, and Tb.Th, while decreasing Tb.Sp and Po. These bioactive YBCH provide a novel strategy for the treatment of osteoporosis, presenting promising applications in nutritional supplements and functional food.