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Hippo signaling is implicated in balancing cell proliferation,   differentiation and death in multiple organs. However, its role in specific   bone cell types such as osteoclasts, and its significance in maintaining   overall bone tissue homeostasis remain largely unknown. In this study, we   investigated the role of the Hippo pathway in osteoclast differentiation.   Human primary monocyte cells were treated with receptor activator nuclear   factor kappaB ligand (RANKL) and evaluated for osteoclast differentiation by   marker protein analysis, tartrate-resistant acid phosphate (TRAP) and   resorption assays. Our results showed that Ste20-like kinase 1 (MST1)   underwent the maximum change after RANKL treatments and is negatively   associated with osteoclast differentiation. Furthermore, proteomic approaches   involving coimmunoprecipitation and mass spectrometry identified MST1   interaction with integrin-linked kinase (ILK) which is lost during RANKL   induced differentiation. Finally, using RNAi and ectopic expression   experiments we observed that MST1-ILK interaction negatively inhibits   osteoclast differentiation at the level of actin ring structure formation,   which is facilitated by ILK. Together, our data highlight a role for the   Hippo pathway protein, MST1, in negatively regulating osteoclast   differentiation through its interaction with integrin signaling. Given that   integrin signaling is progressively implicated in pathological osteolysis,   augmenting this pathway could have therapeutic implications

Hippo signaling protein MST1 regulates osteoclast differentiation by interacting with integrin linked kinase (ILK) and modulating actin structures