AI Article Synopsis
- Glucocorticoid-induced osteoporosis is a significant secondary cause of osteoporosis, and this study investigates the role of elevated Cullin-1 (CUL1) in this condition.
- Using a mouse model, researchers injected dexamethasone to induce osteoporosis and examined bone injury, cell death, and bone formation through various techniques.
- The findings revealed that silencing CUL1 can reduce osteoporosis effects by inhibiting its promotion of ASAP1 degradation, which negatively impacts bone formation and leads to increased cell death.
Article Abstract
Background: Glucocorticoid-induced osteoporosis is a leading secondary cause of osteoporosis. Cullin-1 (CUL1) levels are abnormally elevated in patients with osteoporosis, but the underlying mechanism remains unclear. The purpose of this study was to elucidate the mechanism of action of CUL1 in a glucocorticoid (dexamethasone, Dex)-induced osteoporosis model.
Methods: C57BL/6J mice were intraperitoneally injected with Dex to establish an osteoporosis model. Mouse femur bone injury and bone formation were detected using hematoxylin-eosin or Masson staining. Apoptosis and cell cycle distribution were determined by flow cytometry. Alkaline phosphatase (ALP) activity and calcified nodules were monitored using ALP and Alizarin Red S staining. The molecular mechanism was validated by co-immunoprecipitation (Co-IP) and ubiquitination assays.
Results: CUL1 expression was enhanced in the Dex-induced osteoporosis mouse model. CUL1 silencing moderated the Dex-induced cell proliferation and osteogenesis inhibition. Moreover, CUL1 promoted the ubiquitination and degradation of ASAP1 via the SKP1-CUL1-F-box (SCF)-FBXW7 complex. CUL1 induced apoptosis and repressed osteogenesis by ASAP1. CUL1 silencing alleviated the Dex-induced osteoporosis in mice.
Conclusion: CUL1 suppressed osteoblast proliferation and osteogenesis by promoting ASAP1 ubiquitination via the SCF-FBXW7 complex in glucocorticoid-induced osteoporosis.
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| http://dx.doi.org/10.1007/s42000-024-00599-y | DOI Listing |
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