Gadus morhua is an important commercial fish rich in nutrients required for daily metabolism. However, the regulation of G. morhua peptides (GMP) on osteoblast growth remains unclear. In order to clarify the regulatory effects of GMP on osteoblasts, the effects of GMP on the growth of MC3T3-E1 cells were investigated, and the osteogenic peptides were identified and screened. The results showed that GMP promoted the proliferation and differentiation of osteoblasts by regulating the BMP/WNT signaling pathway at concentrations of 1–100 μg mL?1. Molecular docking studies showed that a decapeptide, MNKKREAEFQ (P-GM-1), had a high affinity for integrins 3VI4 and 1L5G (-CDOCKER interaction energy: 161.30, 212.27 kcal mol?1). Additionally, the proliferation rate of MC3T3-E1 cells was increased by 27%, and ALP activity was significantly increased under P-GM-1 treatment (100 μg mL?1). Moreover, P-GM-1 promotes bone formation, maintains bone homeostasis, and prevents osteoporosis in ovariectomized mice by regulating the BMP/Smad signaling pathway. This study confirmed the potential of GMP in the regulation of bone mineral density and provided a certain theoretical basis for the development of anti-osteoporosis active factors from GMP.
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