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ST5 Positively Regulates Osteoclastogenesis via Src/Syk/calcium Signaling Pathways.


ABSTRACT: For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. In a microarray approach, we found the suppression of tumorigenicity 5 (ST5) gene is upregulated by receptor activator of nuclear factor-?B ligand (RANKL), the OC differentiation factor. Although the roles of ST5 in cancer and ?-cells have been reported, the function of ST5 in bone cells has not yet been investigated. Knockdown of ST5 by siRNA reduced OC differentiation from primary precursors. Moreover, ST5 downregulation decreased expression of NFATc1, a key transcription factor for osteoclastogenesis. In contrast, overexpression of ST5 resulted in the opposite phenotype of ST5 knockdown. In immunocytochemistry experiments, the ST5 protein is colocalized with Src in RANKL-committed cells. In addition, ST5 enhanced activation of Src and Syk, a Src substrate, in response to RANKL. ST5 reduction caused a decrease in RANKL-evoked calcium oscillation and inhibited translocation of NFATc1 into the nucleus. Taken together, these findings provide the first evidence of ST5 involvement in positive regulation of osteoclastogenesis via Src/Syk/calcium signaling.

SUBMITTER: Kim MK 

PROVIDER: S-EPMC6883977 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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ST5 Positively Regulates Osteoclastogenesis via Src/Syk/calcium Signaling Pathways.

Kim Min Kyung MK   Kim Bongjun B   Kwon Jun-Oh JO   Song Min-Kyoung MK   Jung Suhan S   Lee Zang Hee ZH   Kim Hong-Hee HH  

Molecules and cells 20191101 11


For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. In a microarray approach, we found the suppression of tumorigenicity 5 (ST5) gene is upregulated by receptor activator of nuclear factor-κB ligand (RANKL), the OC differentiation factor. Although the roles of ST5 in cancer and β-cells have been reported, the function of ST5 in bone cells has  ...[more]

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