| First Author | Kim EY | Year | 2023 |
| Journal | Cell Biosci | Volume | 13 |
| Issue | 1 | Pages | 48 |
| PubMed ID | 36882866 | Mgi Jnum | J:351584 |
| Mgi Id | MGI:7702345 | Doi | 10.1186/s13578-023-00973-0 |
| Citation | Kim EY, et al. (2023) Dysfunction in parkin aggravates inflammatory bone erosion by reinforcing osteoclast activity. Cell Biosci 13(1):48 |
| abstractText | 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 alpha-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 alpha-tubulin due to failure of interaction with histone deacetylase 6 (HDAC6), which was promoted by IL-1beta signaling. The ectopic expression of parkin in Parkin(-/-) OCPs limited the increase in dentin resorption induced by IL-1beta, accompanied by the reduced acetylation of alpha-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. |
