| First Author | Kobayakawa M | Year | 2020 |
| Journal | Cell Biochem Funct | Volume | 38 |
| Issue | 3 | Pages | 300-308 |
| PubMed ID | 31887784 | Mgi Jnum | J:313249 |
| Mgi Id | MGI:6791517 | Doi | 10.1002/cbf.3476 |
| Citation | Kobayakawa M, et al. (2020) Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas. Cell Biochem Funct 38(3):300-308 |
| abstractText | Podosome formation in osteoclasts is an important initial step in osteoclastic bone resorption. Mice lacking c-Src (c-Src(-/-) ) exhibited osteopetrosis due to a lack of podosome formation in osteoclasts. We previously identified p130Cas (Crk-associated substrate [Cas]) as one of c-Src downstream molecule and osteoclast-specific p130Cas-deficient (p130Cas(DeltaOCL-/-) ) mice also exhibited a similar phenotype to c-Src(-/-) mice, indicating that the c-Src/p130Cas plays an important role for bone resorption by osteoclasts. In this study, we performed a cDNA microarray and compared the gene profiles of osteoclasts from c-Src(-/-) or p130Cas(DeltaOCL-/-) mice with wild-type (WT) osteoclasts to identify downstream molecules of c-Src/p130Cas involved in bone resorption. Among several genes that were commonly downregulated in both c-Src(-/-) and p130Cas(DeltaOCL-/-) osteoclasts, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization. Reduced Kif1c expression was observed in both c-Src(-/-) and p130Cas(DeltaOCL-/-) osteoclasts compared with WT osteoclasts. Kif1c exhibited a broad tissue distribution, including osteoclasts. Knockdown of Kif1c expression using shRNAs in WT osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in p130Cas(DeltaOCL-/-) osteoclasts but not c-Src(-/-) osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas (191 words). SIGNIFICANCE OF THE STUDY: We previously showed that the c-Src/p130Cas (Cas) plays an important role for bone resorption by osteoclasts. In this study, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization, as a downstream molecule of c-Src/p130Cas axis, using cDNA microarray. Knockdown of Kif1c expression using shRNAs in wild-type osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in osteoclast-specific p130Cas-deficient (p130Cas(DeltaOCL-/-) ) osteoclasts but not c-Src(-/-) osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas. |
