The level of Osterix expression in osteoblasts is important to prevent IL6-induced inflammatory-prone state
W. Baek1,2, Y. Kim3, S. Park4, T. Kwon1,2, K. Park1,2 & J. Kim1,2
Osterix (Osx) is an essential transcription factor for osteoblast differentiation and bone formation. Osx null mutants died perinatally with a complete absence of bone formation and Osx conditional knockouts in osteoblasts showed the osteopenic phenotype after birth. Even in Osx heterozygous mice with normal bone morphology, the reduced cortical thickness and osteoblast differentiation were observed by QCT and in vitro cell culture, respectively. This result exhibited that the level of Osx expression was still important for in vivo and in vitro bone formation. Here, we investigated a potential role of Osx to regulate physiological homeostasis in adult tissue. In Osx heterozygous mice with a low expression of Osx in bones, the expression levels of pro-inflammatory cytokines were significantly increased, indicating that their body due to the reduced Osx expression may remain an inflammatory-prone state. Especially, the expression of interleukin (IL)-6, a key mediator of chronic inflammation, was increased in Osx heterozygotes and decreased in Osx overexpressed osteoblastic cells. Kidney as well as bone is one of the most important organs in order to maintain a physiological balance for mineral ions controlled by numerous endocrine factors. The cross-talk between the bone and kidney for physiological homeostasis has been studied for a long time. In Osx heterozygous mice compared to wild-type, no significant difference was observed in renal morphology and urine calcium and phosphate levels. However, the recovery of kidney after ischemic damage was remarkably delayed in Osx heterozygous mice, as indicated by elevated blood urea nitrogen and creatinine levels, and morphological alterations consistent with acute tubular necrosis. Eventually, the low level of Osx expression caused an inflammatory-prone state in the body, resulting in the enhanced susceptibility to renal injury after ischemia/reperfusion. This study suggests that the maintenance of Osx expression in bone is important to prevent inflammatory-prone state. (Grant support: RTI04-01-01, NRF 2010-0008391, BK21)
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.