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- Title
Dysfunction in parkin aggravates inflammatory bone erosion by reinforcing osteoclast activity.
- Authors
Kim, Eun-Young; Kim, Ji-Eun; Kim, Young-Eun; Choi, Bongkun; Sohn, Dong Hyun; Park, Si-On; Chung, Yeon-Ho; Kim, Yongsub; Robinson, William H.; Kim, Yong-Gil; Chang, Eun-Ju
- Abstract
Background: Parkin dysfunction associated with the progression of parkinsonism contributes to a progressive systemic skeletal disease characterized by low bone mineral density. However, the role of parkin in bone remodeling has not yet been elucidated in detail. Result: We observed that decreased parkin in monocytes is linked to osteoclastic bone-resorbing activity. siRNA-mediated knockdown of parkin significantly enhanced the bone-resorbing activity of osteoclasts (OCs) on dentin without any changes in osteoblast differentiation. Moreover, Parkin-deficient mice exhibited an osteoporotic phenotype with a lower bone volume accompanied by increased OC-mediated bone-resorbing capacity displaying increased acetylation of α-tubulin compared to wild-type (WT) mice. Notably, compared to WT mice, the Parkin-deficient mice displayed increased susceptibility to inflammatory arthritis, reflected by a higher arthritis score and a marked bone loss after arthritis induction using K/BxN serum transfer, but not ovariectomy-induced bone loss. Intriguingly, parkin colocalized with microtubules and parkin-depleted-osteoclast precursor cells (Parkin−/− OCPs) displayed augmented ERK-dependent acetylation of α-tubulin due to failure of interaction with histone deacetylase 6 (HDAC6), which was promoted by IL-1β signaling. The ectopic expression of parkin in Parkin−/− OCPs limited the increase in dentin resorption induced by IL-1β, accompanied by the reduced acetylation of α-tubulin and diminished cathepsin K activity. Conclusion: These results indicate that a deficiency in the function of parkin caused by a decrease in parkin expression in OCPs under the inflammatory condition may enhance inflammatory bone erosion by altering microtubule dynamics to maintain OC activity.
- Subjects
TUBULINS; BONE resorption; PARKIN (Protein); BONE density; HISTONE deacetylase; EROSION; BONE remodeling
- Publication
Cell & Bioscience, 2023, Vol 13, Issue 1, p1
- ISSN
2045-3701
- Publication type
Article
- DOI
10.1186/s13578-023-00973-0