Contribution of endoplasmic reticulum stress response to the mechanosensitivity alteration in osteocytes under simulated microgravity

Liu, Li-Jin; Li, Shuang; Wu, Xin-Tong; Yang, Xiao; Sun, Lianwen

doi:10.1016/j.actaastro.2021.11.037

Cited by 1 publication

(1 citation statement)

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“…Uncontrolled ER stress caused by hindlimb suspension for 21 days may have exacerbated osteocyte apoptosis. Liu et alinvestigated the effects of ER stress activation in simulated microgravity that lead to changes in mechano-sensation and apoptosis in osteocytes, and they were able to reduce these effects with an ER stress inhibitor melatonin 62 whereas we were able to reverse the ER stress and downregulated sclerostin expressions using 4-PBA.…”

Section: Discussionmentioning

confidence: 94%

Pharmacological inhibition of endoplasmic reticulum stress mitigates osteoporosis in a mouse model of hindlimb suspension

Al-Daghestani,

Qaisar,

Al Kawas

et al. 2024

Sci Rep

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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.

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Section: Discussionmentioning

confidence: 94%