Oviductus Ranae protein hydrolyzate prevents menopausal osteoporosis by regulating TGFβ/BMP2 signaling

Arch Gynecol Obstet. 2019 Mar;299(3):873-882. doi: 10.1007/s00404-018-5033-9. Epub 2019 Jan 16.


Purpose: It is known that menopausal osteoporosis (MOP) is the most typical form of osteoporosis, which is characterized by low bone mass and microstructure damage of the bone tissue, leading to increased bone fragility and risk of fracture. This study aimed to evaluate the protective effects of Oviductus Ranae protein hydrolyzate (ORPH) on the MOP in vivo.

Methods: Osteoporosis model was induced by ovariectomy, treated with ORPH 150 or 75 mg kg-1. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment, and femoral maximum load was determined immediately after killing. The expression levels of alkaline phosphatase (ALP), Smad4, tartrate acid phosphatase (TRAP), BMP2, Runx2, CPB, ColI and osteocalcin were examined by RT-PCR or western-blotting. HE staining was used to observe the pathological changes in the femurs. Immunohistochemistry was used to detect the expression of ALP and BMP2. All data were analyzed by SPSS 13.0.

Results: The results revealed that ORPH had no effect on the weight of normal and osteoporotic rats. ORPH could significantly improve the femur BMD and increase the maximum load of the osteoporotic rats. ORPH could significantly upregulate the expression level of bone formation makers, ALP, osteocalcin, ColI, and Runx2, and downregulate the expression level of bone resorption marker, TRAP. In the ORPH group, the expression levels of BMP2, Smad4, and CPB of key proteins in the TGFβ/BMP2 signaling pathway were significantly upregulated. In addition, immunohistochemistry showed that ALP and BMP2 expression in femurs of the ORPH group was stranger. H&E staining showed that ORPH (150 mg kg-1) significantly increased the thickness of trabeculae and decreased fracture risk.

Conclusion: Collectively, ORPH plays a role in the prevention and treatment of osteoporosis, which may be a potential anti-osteoporosis drug.

Keywords: ALP; BMD; Menopausal osteoporosis; ORPH; TGFβ/BMP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism*
  • Female
  • Humans
  • Materia Medica / pharmacology
  • Materia Medica / therapeutic use*
  • Osteoporosis, Postmenopausal / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism*


  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Materia Medica
  • Oviductus Ranae
  • Transforming Growth Factor beta1