TY - JOUR
T1 - Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas
AU - Kobayakawa, Miki
AU - Matsubara, Takuma
AU - Mizokami, Akiko
AU - Hiura, Fumitaka
AU - Takakura, Nana
AU - Kokabu, Shoichiro
AU - Matsuda, Miho
AU - Yasuda, Hisataka
AU - Nakamura, Ichiro
AU - Takei, Yosuke
AU - Honda, Hiroaki
AU - Hosokawa, Ryuji
AU - Jimi, Eijiro
N1 - Funding Information:
Grants‐in‐Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Grant/Award Numbers: 18K09509, 26293396 Funding information
Funding Information:
We thank Drs Nobutaka Hirokawa (University of Tokyo, Tokyo, Japan) and Shigeaki Kato (Soma Central Hospital, Fukushima, Japan) for providing the anti‐Kif1c antibody and Cathepsin K‐Cre mice, respectively. This study was supported by the research grant for OBT Research Center from the Kyushu University (to E.J.) and by Grants‐in‐Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (26293396 to E.J. and 18K09509 to T.M.).
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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 (p130CasΔOCL−/−) 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 p130CasΔOCL−/− 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 p130CasΔOCL−/− osteoclasts, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization. Reduced Kif1c expression was observed in both c-Src−/− and p130CasΔOCL−/− 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 p130CasΔOCL−/− 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 (p130CasΔOCL−/−) osteoclasts but not c-Src−/− osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas.
AB - 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 (p130CasΔOCL−/−) 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 p130CasΔOCL−/− 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 p130CasΔOCL−/− osteoclasts, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization. Reduced Kif1c expression was observed in both c-Src−/− and p130CasΔOCL−/− 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 p130CasΔOCL−/− 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 (p130CasΔOCL−/−) osteoclasts but not c-Src−/− osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas.
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U2 - 10.1002/cbf.3476
DO - 10.1002/cbf.3476
M3 - Article
C2 - 31887784
AN - SCOPUS:85078073442
SN - 0263-6484
VL - 38
SP - 300
EP - 308
JO - Cell Biochemistry and Function
JF - Cell Biochemistry and Function
IS - 3
ER -