Skip to main content

Advertisement

Log in

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

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. National Pharmacopoeia Committee (2010) Pharmacopoeia of People’s Republic of China, Part 1. Chinese Medical Science and Technology Press, Beijing, p 239

    Google Scholar 

  2. Mousavi A, Nadjar Araabi B, Nili Ahmadabadi M (2014) Context transfer in reinforcement learning using action-value functions. Comput Intell Neurosci 14:428–433

    Google Scholar 

  3. Wang DH, Wu W, Tian JM, Wang ZH, Wang DT, Xiang K, Zhu GY, Han T (2013) Effect of Oviductus ranae and Oviductus ranae eggs on bone metabolism and osteoporosis. Chin J Integr Med 19(7):532–538

    Article  PubMed  Google Scholar 

  4. Cairoli E, Zhukouskaya VV, Eller-Vainicher C, Chiodini I (2015) Perspectives on osteoporosis therapies. J Endocrinol Investig 38(3):303–309

    Article  CAS  Google Scholar 

  5. Liang L, Zhang XH, Zhou Y, Huang YJ, Deng HZ (2008) Protective effect of Oviductus Ranae capsules on the reproductive organs of aged mice. Nan Fang Yi Ke Da Xue Xue Bao 28:982–985

    PubMed  Google Scholar 

  6. Du X, Xu S, Wang W (1998) Research progress on deglycosylation of mucin glycoprotein. Nat Prod Res Dev 04:94–98

    Google Scholar 

  7. Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656

    PubMed  PubMed Central  Google Scholar 

  8. Melton LJ III, Johnell O, Lau E, Mautelen CA, Seeman E (2004) Osteoporosis and the global competition for health care resources. J Bone Miner Res 19:1055–1058

    Article  PubMed  Google Scholar 

  9. Feldbrin Z, Luckish A, Shargorodsky M (2016) Effects of long-term risedronate treatment on serum ferritin levels in post-menopausal women with osteoporosis: the impact of cardiovascular risk factor load. Menopause 23:55–59

    Article  PubMed  Google Scholar 

  10. Romas E (2005) Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates. Best Pract Res Clin Rheumatol 19:1065–1079

    Article  CAS  PubMed  Google Scholar 

  11. Reid IR (2015) Short-term and long-term effects of osteoporosis therapies. Nat Rev Endocrinol 11:418–428

    Article  CAS  PubMed  Google Scholar 

  12. Cummings SR, Melton JR III (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:176–177

    Article  Google Scholar 

  13. Feng M, Zhang R, Gong F, Yang P, Fan L, Ni J, Bi W, Zhang Y, Wang C, Wang K (2014) Protective effects of necrostatin-1 on glucocorticoid-induced osteoporosis in rats. J Steroid Biochem Mol Biol 144B:455–462

    Article  CAS  Google Scholar 

  14. Samir SM, Malek HA (2014) Effect of cannabinoid receptors 1 modulation on osteoporosis in a rat model of different ages. J Physiol Pharmacol 65:687–694

    CAS  PubMed  Google Scholar 

  15. Jin H, Evangelou E, Ioannidis JPA, Ralston SH (2011) Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies. Osteporos Int 22:911–921

    Article  CAS  Google Scholar 

  16. Rojano-Mejía D, Coral-Vázquez RM, Espinosa LC (2013) JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican Mestizo women. Age 35:471–478

    Article  CAS  PubMed  Google Scholar 

  17. Ji GR, Yao M, Sun CY, Zhang L, Han Z (2009) Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic fracture in Caucasian post-menopausal women: a metaanalysis. J Int Med Res 37:1725–1732

    Article  PubMed  Google Scholar 

  18. Gundberg CM (2000) Biochemical markers of bone formation. Clin Lab Med 20:489–501

    Article  CAS  PubMed  Google Scholar 

  19. Ohara N, Hayashi Y, Yamada S, Kim SK, Matsunaga T (2004) Early gene expression analyzed by cDNA microarray and RT-PCR in osteoblasts cultured with water-soluble and low molecular chitooligosaccharide. Biomaterials 25:1749–1754

    Article  CAS  PubMed  Google Scholar 

  20. Jönsson S, Hjorth-Hansen H, Olsson B, Wadenvik H, Sundan A (2012) Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro. J Bone Miner Metab 30:119–123

    Article  CAS  PubMed  Google Scholar 

  21. Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3:S131–S139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765–771

    Article  CAS  PubMed  Google Scholar 

  23. Otto F, Kanegane H, Mundlos S (2002) Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum Mutat 19:209–216

    Article  CAS  PubMed  Google Scholar 

  24. Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, Shigesada K (2003) Functional analysis of RUNX2 mutations in cleidocranial dysplasia: novel insights into genotype–phenotype correlations. Blood Cells Mol. Dis 30:184–193

    Article  CAS  PubMed  Google Scholar 

  25. Zhang XN, Chen K, Wei B (2016) Ginsenosides Rg3 attenuates glucocorticoid-induced osteoporosis through regulating BMP-2/BMPR1A/Runx2 signaling pathway. Chem Biol Interact 25(6):188–197

    Article  CAS  Google Scholar 

  26. Lee AJ, Hodges S, Eastell R (2000) Measurement of osteocalcin. Ann Clin Biochem 37:432–446

    Article  PubMed  Google Scholar 

  27. Charles P, Poser JW, Mosekilde L, Jensen FT (1985) Estimation of bone turnover evaluated by 47Ca-kinetics. Efficiency of serum bone gamma-carboxyglutamic acid-containing protein, serum alkaline phosphatase, and urinary hydroxy-proline excretion. J Clin Investig 76:2254–2258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Delmas PD, Malaval L, Arlot ME, Meunier PJ (1985) Serum bone Gla-protein compared to bone histomorphometry in endocrine diseases. Bone 6:339–341

    Article  CAS  PubMed  Google Scholar 

  29. Urist MR (1997) Bone morphogenetic protein: the molecularization of skeletal system development. J Bone Miner Res 12:343–346

    Article  CAS  PubMed  Google Scholar 

  30. Medici M, van Meurs JB, Rivadeneira F, Zhao H, Arp PP, Salvatici M, Botteri E (2006) MP-2 gene polymorphisms and osteoporosis: the Rotterdam study. J Bone Miner Res 21(6):845–853

    Article  CAS  PubMed  Google Scholar 

  31. Kanzler B, Foreman RK, Labosky PA, Mallo M (2000) BMP signaling is essential for development of skeletogenic and neurogenic cranial neural crest. Development 127:1095–1104

    CAS  PubMed  Google Scholar 

  32. Spinella-Jaegle S, Roman-Roman S, Faucheu C, Dunn FW, Kawai S, Gallea S, Stiot V, Blanchet AM, Courtois B, Baron R, Rawadi G (2001) Opposite effects of bone morphogenetic Protein-2 and transforming growth factor-1 on osteoblast differentiation. Bone 29:323–330

    Article  CAS  PubMed  Google Scholar 

  33. Thies RS, Bauduy M, Ashton BA, Kurtzberg L, Wozney JM, Rosen V (1992) Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. Endocrinology 130:1318–1324

    CAS  PubMed  Google Scholar 

  34. Zhang H, Bradley A (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122:2977–2986

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by Jilin Province Traditional Chinese Medicine Administration and Jilin Province Department of Education.

Funding

This study was funded by the Jilin Province Traditional Chinese Medicine Science and Technology Project (2017002, 2018024); the Jilin Provincial Department of Education Science Research Project (JJKH20181266KJ); the Jilin province science and technology backbone training project for health and hygiene (2018Q043).

Author information

Authors and Affiliations

Authors

Contributions

XL, XQ and NL conceived and designed the study. XL, XS, QY, and XS performed the experiments. YL provided the Oviductus Ranae. XL wrote the paper. DH, YL, XH, PY and XQ reviewed and edited the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Xiaobo Qu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Sui, X., Yang, Q. et al. Oviductus Ranae protein hydrolyzate prevents menopausal osteoporosis by regulating TGFβ/BMP2 signaling. Arch Gynecol Obstet 299, 873–882 (2019). https://doi.org/10.1007/s00404-018-5033-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-018-5033-9

Keywords

Navigation