Osterix is required for skeletal growth and homeostasis after birth: Implications in osteoporosis
Osteoporosis is a common disorder which affects up to 30% women and 12% men at some point in life. This mostly age-associated disorder has becoming increasingly a major clinical and public health issue as human lifespan increases. Osteoporosis is characterized by reduced bone mass, alterations in bone micro-architecture, reduced bone strength, and elevated risk of fracture (Kanis, 1994). Although both genetic and environmental factors influence the risk of osteoporosis, it has been shown that familial traits are one of the most important clinical risk factors, suggesting the role of genetic factors. The fundamental pathogenic mechanism underlying this disorder includes, (a) failure to achieve peak bone mass during growth and development, (b) excessive bone resorption, and (c) defects in bone formation. Gene knockouts in mice have demonstrated that transcription factors Runx2 and a downstream factor Osterix (Osx) are essential for osteoblast differentiation and bone formation during development. However, little is known about the functions of Runx2 and Osx in postnatal bone growth and homeostasis. In this study, I conditionally inactivated Osx after birth using a tamoxifen-activated cre recombinase. The results showed that Osx is an essential factor for osteoblast differentiation and bone formation both during and after growth periods after birth. In addition, Osx plays a major role in the genetic control of osteocyte function postnatally as well. To date, the emphasis of pharmacotherapy for osteoporosis has been mainly focused on interventions controlling excessive bone resorption. The current study revealed, for the first time, the role of Osx in postnatal osteoblast differentiation and bone formation, providing new insights into the molecular control of postnatal bone growth and homeostasis. It is certain that our results will shed light on developing better preventive and therapeutic procedures for osteoporosis in the future.
Zhou, Xin, "Osterix is required for skeletal growth and homeostasis after birth: Implications in osteoporosis" (2008). Texas Medical Center Dissertations (via ProQuest). AAI3315868.