Al-Daghestani, Hiba and Qaisar, Rizwan and Al Kawas, Sausan and Ghani, Nurhafizah and Rani, K. G. Aghila and Azeem, Muhammad and Hasnan, Hijaz Kamal and Kassim, Nur Karyatee and Samsudin, A. R. (2024) Pharmacological inhibition of endoplasmic reticulum stress mitigates osteoporosis in a mouse model of hindlimb suspension. Scientific Reports, 14 (1). p. 4719. ISSN 2045-2322, DOI https://doi.org/10.1038/s41598-024-54944-7.
Full text not available from this repository.Abstract
Hindlimb suspension (HLS) mice exhibit osteoporosis of the hindlimb bones and may be an excellent model to test pharmacological interventions. We investigated the effects of inhibiting endoplasmic reticulum (ER) stress with 4-phenyl butyrate (4-PBA) on the morphology, physicochemical properties, and bone turnover markers of hindlimbs in HLS mice. We randomly divided 21 male C57BL/6J mice into three groups, ground-based controls, untreated HLS group and 4-PBA treated group (HLS+4PBA) (100mg/kg/day, intraperitoneal) for 21 days. We investigated histopathology, micro-CT imaging, Raman spectroscopic analysis, and gene expression. Untreated HLS mice exhibited reduced osteocyte density, multinucleated osteoclast-like cells, adipocyte infiltration, and reduced trabecular striations on micro-CT than the control group. Raman spectroscopy revealed higher levels of ER stress, hydroxyproline, non-collagenous proteins, phenylalanine, tyrosine, and CH2Wag as well as a reduction in proteoglycans and adenine. Furthermore, bone alkaline phosphatase and osteocalcin were downregulated, while Cathepsin K, TRAP, and sclerostin were upregulated. Treatment with 4-PBA partially restored normal bone histology, increased collagen crosslinking, and mineralization, promoted anti-inflammatory markers, and downregulated bone resorption markers. Our findings suggest that mitigating ER stress with 4-PBA could be a therapeutic intervention to offset osteoporosis in conditions mimicking hindlimb suspension.
| Item Type: | Article |
|---|---|
| Funders: | University of Sharjah, Raman analysis and Mrs. Nival, Faculty of Science, Universiti Malaya |
| Uncontrolled Keywords: | 4-PBA; ER stress; HLS mice; Osteoporosis; Bone resorption |
| Subjects: | Q Science > Q Science (General) |
| Divisions: | Faculty of Science > Department of Geology |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 28 Oct 2024 08:14 |
| Last Modified: | 28 Oct 2024 08:14 |
| URI: | http://eprints.um.edu.my/id/eprint/45552 |
Actions (login required)
 |
View Item |
