Sialoglycoproteins Isolated from the Eggs of Gadus morhua Inhibit Bone Resorption in Ovariectomized Rats by Suppressing the MAPK and NF-κB Pathways

The present study investigated the anti-osteoporosis function and the mechanism of sialoglycoproteins isolated from the eggs of Gadus morhua (Gm-SGP) on ovariectomized (OVX) rats. After 3 months of Gm-SGP treatment, OVX-induced bone loss was suppressed and uncoupling bone turnover was balanced, as indicated by systemic biomarkers of bone metabolism; no uterine estrogenicity was observed. Moreover, rats administered with Gm-SGP exhibited increased bone mineral density and biomechanical strength and significant restoration of the trabecular microarchitecture compared with rats in the control group. Gm-SGP significantly decreased bone resorption-related indicators in serum. Investigation of the associated mechanisms revealed that Gm-SGP significantly increases the OPG/RANKL ratio at the mRNA and protein levels. Further research suggested that Gm-SGP inhibits the mRNA and protein expressions of important transcription factors of the MAPK and NF-κB signaling pathways. It also attenuates the activation of related transduction signaling pathways by inhibiting phosphorylation of JNK, ERK, p38, and NF-κB, and ultimately suppresses the induction of c-Fos and NFATc1. Overall, these results demonstrate that Gm-SGP inhibits bone resorption by suppressing osteoclastogenesis-related MAPK and NF-κB pathways, thereby improving osteoporosis.