Mechanical loading activates the YAP/TAZ pathway and chemokine expression in the MLO-Y4 osteocyte-like cell line

Osteocytes are mechanosensitive cells that control bone remodeling in response to mechanical loading. To date, specific signaling pathways modulated by mechanical loading in osteocytes are not well understood. Yes associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the main effectors of the Hippo pathway, are reported to play a role in mechanotransduction and during osteoblastogenesis. Here, we hypothesized that YAP/TAZ signaling mediates osteocyte mechanosensing to target genes of the bone remodeling process. We aimed to investigate the contribution of YAP/TAZ in modulating the gene expression in an osteocyte-like cell line MLO-Y4. We developed a 3D osteocyte compression culture model from an MLO-Y4 osteocyte cell line embedded in concentrated collagen hydrogel. 3D-mechanical loading led to the increased expression of mechanosensitive genes and a subset of chemokines, including M-csf, Cxcl1, Cxcl2, Cxcl3, Cxcl9, and Cxcl10. The transcription regulators YAP and TAZ translocated to the nucleus and upregulated their target genes and proteins. RNAseq analysis revealed that YAP/TAZ knockdown mediated the regulation of several genes including osteocyte dendrite formation. Use of YAP/TAZ knockdown partially blunted the increase in M-csf and Cxcl3 levels in response to MLO-Y4 compression. These findings demonstrate that YAP/TAZ signaling is required for osteocyte-like cell mechano-transduction, regulates the gene expression profiles and controls chemokine expression. The authors investigated the contribution of yes associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in osteocyte mechanotransduction. In a 3-D osteocyte compression model, they show that YAP/TAZ signaling is activated, is required for osteocyte mechano-responsiveness, and regulates the expression profile of target genes as shown by RNAseq analysis and the control of chemokine expression.

Automated summary

The authors investigated the role of Yes associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in osteocyte mechanotransduction. Using a 3D osteocyte compression model, they demonstrated that YAP/TAZ signaling is activated, essential for osteocyte mechano-responsiveness, and regulates gene expression profiles through RNAseq analysis and control of chemokine expression.