Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice.
The transcription factor Osterix (Osx) is required for osteoblast differentiation and bone formation during embryonic development, but it is not known whether Osx has an essential function in postnatal bone growth and in bone homeostasis. Conditional deletion of Osx at several time points postnatally revealed that Osx was essential for osteoblast differentiation and new bone formation in growing and adult bones. Additionally, inactivation of Osx in bones severely disrupted the maturation, morphology, and function of osteocytes. These findings identify Osx as having an essential role in the cell-specific genetic program of osteocytes. Interestingly, Osx inactivation also led to the massive accumulation of unresorbed calcified cartilage in a large area below the growth plate of endochondral bones. This specific area was also marked by an unanticipated almost complete lack of bone marrow cells and a marked decrease in the density and size of osteoclasts. This diminished density of osteoclasts could contribute to the lack of resorption of mineralized cartilage. In addition, we speculate that the abnormally accumulated, mainly naked cartilage represents an unfavorable substrate for osteoclasts. Our study identifies Osx as an essential multifunctional player in postnatal bone growth and homeostasis.
Zhou
Xin
X
Department of Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Zhang
Zhaoping
Z
Feng
Jian Q
JQ
Dusevich
Vladmir M
VM
Sinha
Krishna
K
Zhang
Hua
H
Darnay
Bryant G
BG
de Crombrugghe
Benoit
B
D000818:Animals; D000831:Animals, Newborn; D001846:Bone Development; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002113:Calcification, Physiologic; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D006706:Homeostasis; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010012:Osteogenesis; D010641:Phenotype; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*
D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors