Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species

mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation

“…STAT1 is a known substrate of mTORC1 (38,39) and unphosphorylated STAT1 has been shown to attenuate Runx2 activity by retaining Runx2 in the cytoplasm (40). STAT3 is essential for normal skeletal development (41,42), and STAT3 activation (serine 727 phosphorylation) is dependent on mTORC1 activity (43). Based on these findings, we investigated the phosphorylation status of STAT1 and STAT3 in control and Rptor-null osteoblasts, and this revealed no significant change in the phosphorylation status of Ser727 of either protein in control Ϫ/Ϫ mice were cultured under osteogenic conditions, and the levels of acid-soluble mineral were quantified and expressed relative to the total DNA.…”

Stat3 Signaling Cascade in the Differentiation, Growth and Functions of Bone Cells

“…Osteoblasts from the calvaria were cultured and assayed to evaluate the different levels of ROS compared to those of wild-type mice. The ROS levels were shown to be significantly higher in the Stat3knockout mice compared to those of the control mice [24]. The high levels of ROS appear to negatively affect in vivo bone formation in response to mechanical stress, as evidenced by the reduction of load-induced bone formation in these conditional Stat3KO mice in comparison with the controls.…”

“…This raises interesting questions on what effect the inappropriate function of the electron transport chain would have when Stat3 is knocked down. To test this, Zhou et al [24] generated bone-selective Stat3 knockout mice, in which Stat3 is specifically inactive in osteoblasts and osteocytes, and performed in vivo mechanical loading on their right ulnas. These bone cell-specific Stat3-deficient mice had significantly reduced body stature and weight, with femur lengths showing the most marked disparities.…”

Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3

“…Mutations in STAT3 result in Job syndrome characterised by skeletal and craniofacial anomalies [52]. Furthermore, the ability of autologous serum, a rich source of LPA, to promote osteoblast formation from human mesenchymal cells was found to be accompanied by enhanced STAT3…”