Skip to main content

Advertisement

SpringerLink
Log in

The potential anti-osteoporotic effect of exercise—induced increased preptin level in ovariectomized rats

  • Original Article
  • Published:
Anatomical Science International Aims and scope Submit manuscript

Abstract

Osteoporosis increases bone fragility and fractures. Preptin hormone is regulated by moderate exercise training and increases bone formation. Therefore, this study was conducted to see how estradiol administration and moderate exercise training affected osteoporotic changes in ovariectomized (OVX) rats. To achieve this aim, 36 healthy adult female Wistar albino rats were randomized into Sham, OVX, ovariectomized estradiol-treated (OVX + E) (OVX + E rats were treated using subcutaneous estradiol benzoate 2.5 μg/kg body weight/day), ovariectomized practicing moderate exercise training, ovariectomized estradiol-treated and practiced a moderate exercise training, and ovariectomized alendronate-treated (OVX + Alen) (OVX + Alen rats were treated orally with alendronate 3 mg/kg body weight/week) groups. Alendronate was used as a standard anti-osteoporotic drug. Moderate exercise training, including therapy with estradiol and alendronate for OVX rats began on the fourth week and lasted for six weeks. Results showed that OVX rats had estrogen and preptin deficiency in serum. These deficiencies were associated with a significant increase in bone resorption biomarkers (urinary deoxypyridinoline and hydroxyproline), and bone formation biomarkers (serum osteocalcin and bone-specific alkaline phosphatase). Also, serum pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) were increased, while bone osteopontin (OPN) expression was decreased. Subsequently, the osteoporotic alterations were verified based on histopathological changes. From the results, estradiol therapy and moderate exercise training significantly improved these findings to the same extent as that of the standard alendronate treatment. Therefore, through their anti-inflammatory properties, increasing bone OPN expression, and regulating serum preptin; estradiol therapy and moderate exercise training can reduce osteoporotic alterations in OVX rats. Thus, combined estradiol therapy and moderate exercise training could be a promising potential therapeutic protocol to reduce postmenopausal osteoporosis. Also, targeting serum preptin and bone osteopontin regulation could have a critical role in the treatment of postmenopausal osteoporosis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Abdel-Sater K, Mansour H (2012) Effects of leptin on metabolic bone turnover in ovariectomy rats. Acta Endocrinol 1841–0987:8

    Google Scholar 

  • Abdel-Sater KA, Mansour H (2013) Bone biomarkers of ovariectomised rats after leptin therapy. Bratisl Lek Listy 114:303–307

    CAS  Google Scholar 

  • Abu Taleb OM, Wissa MY, Abou El Nour RK, Awad HA, Moussa NM (2020) Potential effectiveness of exenatide in experimentally-induced osteoporosis. Egypt Rheumatol 42:57–62

    Article  Google Scholar 

  • Abuohashish HM, Ahmed MM, Al-Rejaie SS, Eltahir KEH (2015) The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model. Acta Pharmacol Sin 36:209–220

    Article  CAS  Google Scholar 

  • Ahn N, Kim K (2016) Effects of 12-week exercise training on osteocalcin, high-sensitivity C-reactive protein concentrations, and insulin resistance in elderly females with osteoporosis. J Phys Ther Sci 28:2227–2231

    Article  Google Scholar 

  • Aydin S, Celik O, Gurates B et al (2013) Concentrations of preptin, salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus. Peptides 49:123–130

    Article  CAS  Google Scholar 

  • Baloğlu M, Özkorkmaz EG (2019) Biochemical and immunohistochemical investigations on bone formation and remodelling in ovariectomised rats with tamoxifen citrate administration. Folia Morphol 78:789–797

    Article  Google Scholar 

  • Bancroft J, Stevens A (2013) Theories and practice of histological techniques.) New York, London and Madrid: Churchil Livingstone

  • Bebars GM, Sallam SA, Gaber SS, Abdelaziz AH (2019) Assessment of Preptin peptide level in the sera of rachitic children and in breast milk of their mothers. Ital J Pediatr 45:34

    Article  Google Scholar 

  • Bergendal A, Kieler H, Sundström A, Hirschberg AL & Kocoska-Maras L (2016) Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration. Menopause (New York, N.Y.) 23, 593–9.

  • Byun JS, Lee SS (2010) Effect of soybeans and sword beans on bone metabolism in a rat model of osteoporosis. Ann Nutr Metab 56:106–112

    Article  CAS  Google Scholar 

  • Chen Y-J, Huang C-H, Lee I-C, Lee Y-T, Chen M-H, Young T-H (2008) Effects of cyclic mechanical stretching on the mRNA expression of tendon/ligament-related and osteoblast-specific genes in human mesenchymal stem cells. Connect Tissue Res 49:7–14

    Article  CAS  Google Scholar 

  • Chen S-Y, Yu H-T, Kao J-P et al (2014) An NMR metabolomic study on the effect of alendronate in ovariectomized mice. PLoS One 9:e106559

    Article  Google Scholar 

  • Cornish J, Callon KE, Bava U et al (2007) Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo. American journal of physiology. Endocrinol Metab 292:E117–E122

    CAS  Google Scholar 

  • Da Paz L, De Falco V, Teng N, Dos Reis L, Pereira R, Jorgetti V (2001) Effect of 17ß-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats. Braz J Med Biol Res 34:1015–1022

    Article  Google Scholar 

  • Daly RM, Dalla Via J, Duckham RL, Fraser SF, Helge EW (2019) Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription. Braz J Phys Ther 23:170–180

    Article  Google Scholar 

  • Ducy P, Amling M, Takeda S et al (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207

    Article  CAS  Google Scholar 

  • El-Haroun H, Soliman M, El-Gawad A (2020) Comparative study on the possible protective effect of lepidium sativum versus teriparatide in induced osteoporosis in adult male Guinea pigs. Egypt J Histol 43:931–947

    Google Scholar 

  • Felsenberg D, Boonen S (2005) The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27:1–11

    Article  Google Scholar 

  • Feng R, Wang L, Li Z et al (2019) A systematic comparison of exercise training protocols on animal models of cardiovascular capacity. Life Sci 217:128–140

    Article  CAS  Google Scholar 

  • Fodor D, Bondor C, Albu A, Simon S-P, Craciun A, Muntean L (2013) The value of osteopontin in the assessment of bone mineral density status in postmenopausal women. J Investig Med 61:15–21

    Article  CAS  Google Scholar 

  • Gallo D, Zannoni GF, Apollonio P, et al. (2005) Characterization of the pharmacologic profile of a standardized soy extract in the ovariectomized rat model of menopause: effects on bone, uterus, and lipid profile. Menopause (New York, N.Y.) 12, 589–600.

  • Halasy-Nagy J, Rodan G, Reszka A (2001) Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. Bone 29:553–559

    Article  CAS  Google Scholar 

  • Heather B, Karen J (2002) Estrogen replacement reverses ovariectomy-induced vaginal hyperalgesia in the rat. Maturitas 41:157–165

    Article  Google Scholar 

  • Heilmeier U, Youm J, Torabi S, Link TM (2016) Osteoporosis imaging in the geriatric patient. Curr Radiol Rep 4:18

    Article  Google Scholar 

  • Honjo S, Mizunuma H, Soda M, Igarashi M (1989) Effect of estrogen replacement therapy on the serum osteocalcin level in the postmenopausal and castrated women. Nihon Sanka Fujinka Gakkai Zasshi 41:1571–1576

    CAS  Google Scholar 

  • Ibm II (2017) Statistics for Windows, Version 25.0. Armonk, NY: IBM Corporation.

  • Kanis JA, Gertz B, Singer F, Ortolani S (1995) Rationale for the use of alendronate in osteoporosis. Osteoporos Int 5:1–13

    Article  CAS  Google Scholar 

  • Kanjana K, Haygarth KS, Wu W, Bartels DM (2013) Laboratory studies in search of the critical hydrogen concentration. Radiat Phys Chem 82:25–34

    Article  CAS  Google Scholar 

  • Kim BT, Mosekilde L, Duan Y et al (2003) The structural and hormonal basis of sex differences in peak appendicular bone strength in rats. J Bone Mineral Res 18:150–155

    Article  CAS  Google Scholar 

  • Kitaura H, Marahleh A, Ohori F et al (2020) Osteocyte-related cytokines regulate osteoclast formation and bone resorption. Int J Mol Sci 21:5169

    Article  CAS  Google Scholar 

  • Kolios L, Hoerster AK, Sehmisch S et al (2010) Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis? Calcif Tissue Int 86:23–32

    Article  CAS  Google Scholar 

  • Lasota A, Danowska-Klonowska D (1995) (2004) Experimental osteoporosis–different methods of ovariectomy in female white rats. Rocz Akad Med Bialymst 49(Suppl 1):129–131

    Google Scholar 

  • Lee K, Jessop H, Suswillo R, Zaman G, Lanyon L (2003) Bone adaptation requires oestrogen receptor-α. Nature 424:389–389

    Article  CAS  Google Scholar 

  • Li N, Zheng YB, Han J et al (2013) Lower circulating preptin levels in male patients with osteoporosis are correlated with bone mineral density and bone formation. BMC Musculoskelet Disord 14:49

    Article  CAS  Google Scholar 

  • Mierzwicka A, Kuliczkowska-Plaksej J, Kolačkov K, Bolanowski M (2018) Preptin in women with polycystic ovary syndrome. Gynecol Endocrinol 34:470–475

    Article  CAS  Google Scholar 

  • Miller FN, Wiegman DL (1977) Anesthesia-induced alteration of small vessel response to norepinephrine. Eur J Pharmacol 44:331–337

    Article  CAS  Google Scholar 

  • Mohammad Rahimi GR, Bijeh N, Rashidlamir A (2020) Effects of exercise training on serum preptin, undercarboxylated osteocalcin and high molecular weight adiponectin in adults with metabolic syndrome. Exp Physiol 105:449–459

    Article  CAS  Google Scholar 

  • Müller ST, Keiler AM, Kräker K, Zierau O, Bernhardt R (2018) Influence of estrogen on individual exercise motivation and bone protection in ovariectomized rats. Lab Anim 52:479–489

    Article  Google Scholar 

  • Mustafa RA, NaA A, Hijazi HH, Header EA, Azzeh FS (2018) Biological effect of calcium and vitamin D dietary supplements against osteoporosis in ovariectomized rats. Prog Nutr 20:86–93

    CAS  Google Scholar 

  • Nazari Soltan Aahmad S, Nourollahi S, Kazerouni F et al (2018) Investigation of the relation between bone mass density and serum preptin levels in pre- and postmenopausal women. J Bone Miner Metab 36:710–715

    Article  CAS  Google Scholar 

  • Notomi T, Okimoto N, Okazaki Y, Nakamura T, Suzuki M (2003) Tower climbing exercise started 3 months after ovariectomy recovers bone strength of the femur and lumbar vertebrae in aged osteopenic rats. J Bone Mineral Res 18:140–149

    Article  Google Scholar 

  • Novelli E, Diniz Y, Galhardi C et al (2007) Anthropometrical parameters and markers of obesity in rats. Lab Anim 41:111–119

    Article  CAS  Google Scholar 

  • Osman AS, Aly Labib DA, Omar AI (2018) Do acid suppressive drugs (pantoprazole and ranitidine) attenuate the protective effect of alendronate in estrogen-deficient osteoporotic rats? Egypt Rheumatol 40:99–106

    Article  Google Scholar 

  • Osterhoff G, Morgan EF, Shefelbine SJ, Karim L, Mcnamara LM, Augat P (2016) Bone mechanical properties and changes with osteoporosis. Injury 47:S11–S20

    Article  Google Scholar 

  • Ozkan Y, Timurkan ES, Aydin S et al (2013) Acylated and desacylated ghrelin, preptin, leptin, and nesfatin-1 Peptide changes related to the body mass index. Int J Endocrinol 2013:236085–236085

    Article  Google Scholar 

  • Özşahin ETT, Çam B, Dere F et al (2017) The effect of alendronate sodium on trabecular bone structure in an osteoporotic rat model. Turkish J Phys Med Rehabil 63:165

    Article  Google Scholar 

  • Popović T, Šrbić R, Matavulj M, Obradović Z & Sibinčić S (2016) Experimental model of osteoporosis on 14 weeks old ovariectomised rats: biochemical, histological and biomechanical study. Biologia Serbica 38.

  • Pytlik M, Kaczmarczyk-Sedlak I, Sliwiński L, Janiec W, Rymkiewicz I (2004) Effect of concurrent administration of alendronate sodium and retinol on development of changes in histomorphometric parameters of bones induced by ovariectomy in rats. Pol J Pharmacol 56:571–579

    CAS  Google Scholar 

  • Röhling M, Herder C, Stemper T & Müssig K (2016) Influence of acute and chronic exercise on glucose uptake. J Diabet Res

  • Salazar M, Hernandes L, Ramos AL et al (2015) Effect of alendronate sodium on tooth movement in ovariectomized rats. Arch Oral Biol 60:776–781

    Article  CAS  Google Scholar 

  • Sharaf H, Shaffie N, Morsy F, Badawi M, Abbas N (2015) Role of some phytoestrogens in recovering bone loss: histological results from experimental ovariectomized rat models. J Arab Soc Med Res 10:65–75

    Article  Google Scholar 

  • Silva J, Fernandes T, Soci UP, Monteiro AW, Phillips MI, Em DEO (2012) Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis. Med Sci Sports Exerc 44:1453–62

    Article  Google Scholar 

  • Singh A, Gill G, Kaur H, Amhmed M, Jakhu H (2018) Role of osteopontin in bone remodeling and orthodontic tooth movement: a review. Prog Orthod 19:1–8

    Article  Google Scholar 

  • Stachenfeld NS (2014) Hormonal changes during menopause and the impact on fluid regulation. Reproduct Sci (Thousand Oaks, Calif.) 21: 555–561

  • Stavropoulou A, Christopoulou GE, Anastassopoulos G et al (2005) Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats. Clin Chem Lab Med 43:1359–1365

    Article  CAS  Google Scholar 

  • Sun X, Fengbo L, Xinlong M et al (2015) The effects of combined treatment with naringin and treadmill exercise on osteoporosis in ovariectomized rats. Sci Rep 5:1–9

    Google Scholar 

  • Surve VV, Andersson N, Lehto-Axtelius D, Håkanson R (2001) Comparison of osteopenia after gastrectomy, ovariectomy and prednisolone treatment in the young female rat. Acta Orthop Scand 72:525–532

    Article  CAS  Google Scholar 

  • Suzuki N, Yoshimura Y, Deyama Y, Suzuki K, Kitagawa Y (2008) Mechanical stress directly suppresses osteoclast differentiation in RAW264. 7 cells. Int J Mol Med 21:291–296

    CAS  Google Scholar 

  • Taherdoost H (2016) Sampling methods in research methodology; how to choose a sampling technique for research. How to Choose a Sampling Technique for Research

  • Tanaka S, Narusawa K, Onishi H et al (2011) Lower osteocalcin and osteopontin contents of the femoral head in hip fracture patients than osteoarthritis patients. Osteoporos Int 22:587–597

    Article  CAS  Google Scholar 

  • Tomeleri CM, Ribeiro AS, Souza MF et al (2016) Resistance training improves inflammatory level, lipid and glycemic profiles in obese older women: A randomized controlled trial. Exp Gerontol 84:80–87

    Article  CAS  Google Scholar 

  • Turkozan N, Ulusoy A, Balcioglu H, Bal F, Ozel S (2009) The effects of ovariectomy and naproxen treatment on the strength of femoral midshaft and molar alveolar region in rats. Int J Morphol 27:659–666

    Article  Google Scholar 

  • Weitzmann MN, Pacifici R (2006) Estrogen deficiency and bone loss: an inflammatory tale. J Clin Investig 116:1186–1194

    Article  CAS  Google Scholar 

  • Xiao C, Li W, Lu T, Wang J, Han J (2019) Preptin promotes proliferation and osteogenesis of MC3T3-E1 cells by upregulating β-catenin expression. IUBMB Life 71:854–862

    CAS  Google Scholar 

  • Xiong H, Wei L, Hu Y, Zhang C, Peng B (2010) Effect of alendronate on alveolar bone resorption and angiogenesis in rats with experimental periapical lesions. Int Endod J 43:485–491

    Article  CAS  Google Scholar 

  • Yarrow JF, Mccoy SC, Ferreira JA et al (2012) A rehabilitation exercise program induces severe bone mineral deficits in estrogen deficient rats following extended disuse. Menopause (New York, NY) 19:1267

    Article  Google Scholar 

  • Yoon K-H, Cho D-C, Yu S-H, Kim K-T, Jeon Y, Sung J-K (2012) The change of bone metabolism in ovariectomized rats : analyses of microct scan and biochemical markers of bone turnover. J Korean Neurosurg Soc 51:323–327

    Article  Google Scholar 

Download references

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

  1. Physiology Department, Faculty of Medicine, Zagazig University, Zagazig, 44511, Egypt

    Khaled Abdelfattah Abulfadle, Rania Refaat Abdelkader Atia & Nourelhuda A. Mohammed

  2. Basic Medical Science Department, Faculty of Applied Medical Science, Albaha University, Albaha, 65511, Saudi Arabia

    Rania Refaat Abdelkader Atia

  3. Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, 44511, Egypt

    Heba Osama Mohammed & Rania Saad Ramadan

  4. Physiology and Biochemistry Department, Mut’ah School of Medicine, Mut’ah University, Mut’ah, 61710, Al-Karak, Jordan

    Nourelhuda A. Mohammed

Authors
  1. Khaled Abdelfattah Abulfadle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rania Refaat Abdelkader Atia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heba Osama Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rania Saad Ramadan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nourelhuda A. Mohammed
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed in research design and interpretation of the studies. KAA, HOM, and NAM conducted experiments and performed data analysis. KAA, RRAA, RSR, and NAM contributed to review and writing of the manuscript. All individuals contributed in this research are included in the list of authors.

Corresponding author

Correspondence to Nourelhuda A. Mohammed.

Ethics declarations

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdelfattah Abulfadle, K., Refaat Abdelkader Atia, R., Osama Mohammed, H. et al. The potential anti-osteoporotic effect of exercise—induced increased preptin level in ovariectomized rats. Anat Sci Int 98, 22–35 (2023). https://doi.org/10.1007/s12565-022-00666-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12565-022-00666-7

Keywords

Search

Navigation