Abstract
Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoblasts secrete matrix, with some being buried within the newly formed bone, and differentiate to osteocytes. During embryogenesis, bones are formed through intramembraneous or endochondral ossification. The former involves a direct differentiation of mesenchymal progenitor to osteoblasts, and the latter is through a cartilage template that is subsequently converted to bone. Advances in lineage tracing, cell sorting, and single-cell transcriptome studies have enabled new discoveries of gene regulation, and new populations of skeletal stem cells in multiple niches, including the cartilage growth plate, chondro-osseous junction, bone, and bone marrow, in embryonic development and postnatal life. Osteoblast differentiation is regulated by a master transcription factor RUNX2 and other factors such as OSX/SP7 and ATF4. Developmental and environmental cues affect the transcriptional activities of osteoblasts from lineage commitment to differentiation at multiple levels, fine-tuned with the involvement of co-factors, microRNAs, epigenetics, systemic factors, circadian rhythm, and the microenvironments. In this review, we will discuss these topics in relation to transcriptional controls in osteogenesis.
Highlights
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The progenitor cells will differentiate into osteoblasts or chondrocytes for intramembranous and endochondral ossification, respectively (Figure 1B)
Osteochondroprogenitors in limb buds, expressing PRRX1 and low levels of SOX9 that give rise to the cartilage template of long bones, are distinct to a nebuoranlescraerset-gdeenreivreadtedpofrpoumlattihoennieduernatlifcireedstinancdalpvaarriaaxliablomneessofrdoemrma; ahnudmtahne eamppbernyodi[c5u]l.ar Fusrktheleert,ounsiinsgdRerNivAedvefrloomcitythaenlaaltyesriaslfpolrattheemaessseosdsemrmen[t1o–f3c].elSluklealertsatladteehvieelroaprmcheynot rbeligni-ns eawgei,thosmteigorcahtoionndroofpmroesgeenncihtoyrms afrlocmellsthteo ltihme bsitbeusdofcfauntubree sbpoenceisfi,eadndinstkoeeleitthael relRemUeNnXts2+are osttheoengefnoircmoerdSvOiXa 9e+ithcheronindtrroamgeenmicblrianneoaugseso[s5s]ifi. cation or endochondral ossification, both of which begin with the mesenchymal cell condensation [4] (Figure 1A)
Summary
Our skeleton does provide mechanical support to facilitate locomotion and protect our internal organs. It is a major reservoir of calcium and phosphate in our body. Our knowledge of bone biology has expanded with advances in molecular cell technologies. Single-cell transcriptomic and in vivo cell lineage technologies have transformed our ability to identify novel transcription factor pathway interactions in osteogenesis. New cell types such as skeletal stem cells (SSCs), recycling of osteoclasts via osteomorphs, and different sources of osteoblasts in development and growth have been identified. We will discuss recent advances in bone biology, and new findings on the genetic regulation of the osteogenic lineage
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