Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 21.
doi: 10.1007/s00210-025-04145-4. Online ahead of print.

Anti-osteoporotic effect of sitagliptin in an osteoporosis model of ovariectomized rats: role of RUNX2 and RANKL/OPG ratio

Salma Ahmed El-Marasy  1 , Rehab F Abdel-Rahman  2 , Reham M Abd-Elsalam  3 , Hanan A Ogaly  4 , Rasha M Allam  2
Affiliations

Anti-osteoporotic effect of sitagliptin in an osteoporosis model of ovariectomized rats: role of RUNX2 and RANKL/OPG ratio

Salma Ahmed El-Marasy et al. Naunyn Schmiedebergs Arch Pharmacol. .

Abstract

This study examines the potential anti-osteoporotic effect of sitagliptin in osteoporosis instigated by ovariectomy (OVX) in rats. Rats were assigned into 4 groups: Sham-operated, OVX group, and OVX rats orally treated with sitagliptin (10, 20 mg/kg), respectively, after 8 weeks of OVX for 4 weeks. Biochemical, real-time polymerase chain reaction, histopathological, and immunohistochemical analyses of bone resorption and formation were conducted. Sitagliptin ameliorated bone mineral density (BMD), restored calcium and phosphorus levels in OVX rats, elevated catalase and decreased malondialdehyde, reduced receptor activator of NF-κB ligand (RANKL), elevated osteoprotegerin (OPG), and reduced tartrate-resistant acid phosphatase (TRAP) femur contents. Sitagliptin mitigated variations in mRNA expressions of RUNX2 and protein kinase B (AKT) in femur tissue. Moreover, sitagliptin reduced caspase-3 protein expression and improved bone histomorphology and mechanical properties. Sitagliptin's anti-oxidant activity mediated its anti-osteoporotic effect in OVX rats via modulation of RUNX2, downregulation of RANKL/OPG, AKT pathways, apoptosis, and histomorphometry alterations revealing attenuation of osteoclastogenesis and promotion of osteoblast formation.

Keywords: Ovariectomy; RANKL/OPG; RUNX2; Rats; Sitagliptin; TRAP.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: All animal procedures adhered to the ARRIVE guidelines and received approval from the Ethical Committee of Medical Research, National Research Centre, no. 14110112021. Consent to participate: N/A. Consent for publication: N/A. Competing interests: The authors declare no competing interests.

Similar articles

See all similar articles

References

    1. Abu-Elala NM, Abd-Elsalam RM, Marzouk MS (2015) Molecular and immunohistochemical diagnosis of Photobacterium damselae subspecies piscicida during naturally occurring disease in Egypt. J World Aquacult Soc 46:583–595 - DOI
    1. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/s0076-6879(84)05016-3 - DOI - PubMed
    1. Arafa EA, Elgendy NO, Elhemely MA, Abdelaleem EA, Mohamed WR (2023) Diosmin mitigates dexamethasone-induced osteoporosis in vivo: role of Runx2, RANKL/OPG, and oxidative stress. Biomed Pharmacother 161:114461. https://doi.org/10.1016/j.biopha.2023.114461 - DOI - PubMed
    1. Chen D, Wang Q, Li Y, Sun P, Kuek V, Yuan J, Yang J, Wen L, Wang H, Xu J, Chen P (2021) Notopterol Attenuates estrogen deficiency-induced osteoporosis via repressing RANKL signaling and reactive oxygen species. Front Pharmacol 12:664836. https://doi.org/10.3389/fphar.2021.664836 - DOI - PubMed - PMC
    1. Cheng Y, Liu P, Xiang Q, Liang J, Chen H, Zhang H, Yang L (2022b) Glucagon-like peptide-1 attenuates diabetes-associated osteoporosis in ZDF rat, possibly through the RAGE pathway. BMC Musculoskelet Disord 23:465. https://doi.org/10.1186/s12891-022-05396-5 - DOI - PubMed - PMC

LinkOut - more resources