OBJECTIVE To investigate the effects of the polypeptide HAIYPRH(HAI) on ovariectomized(OVX) osteoporotic(OP) mice.

METHODS Thirty 8-week-old SPF-grade female C57BL/6J mice were randomly divided into sham operation group, model group, estradiol benzoate group(0.2 mg·kg⁻¹), and low-dose(60 mg·kg⁻¹) and high-dose(120 mg·kg⁻¹) of HAI groups, with 6 mice in each group. Except for the sham operation group, the other groups underwent bilateral ovariectomy to establish the OP model. Drugs were administered intraperitoneally once every 2 d for 3 months. Bone mineral density(BMD), bone mineral content(BMC), bone microstructural parameters, and serum metabolic indicators were measured, combined with histomorphological observations and immunohistochemical staining, to assess the bone-protective effects of HAI on OP mice.

RESULTS Compared with the sham operation group, the model group showed decreased BMD, impaired bone microstructure, and reduced levels of bone formation markers, indicating successful modeling. Compared with the model group, HAI significantly improved femoral bone microstructure, increased BMD, and elevated the levels of bone formation markers such as bone alkaline phosphatase, procollagen type I N-terminal propeptide, and osteocalcin. Additionally, HAI upregulated the protein expression of runt-related transcription factor 2 and osteopontin. Furthermore, HAI had no adverse effects on the major organs of the mice.

CONCLUSION HAI can promote bone formation in OP mice, elevate femoral BMD, and improve femoral bone microarchitecture, thereby achieving the effect of preventing and treating OP. At the dosage adopted in this study, HAI shows no adverse effects on OP mice, which provides a reference for the subsequent development of related products.