Abstract
Corticalization, coalescence of trabecular bone into the metaphyseal cortex, is important for the longitudinal growth of long bones. However, little is known about the molecular mechanisms controlling corticalization. To understand the molecular mechanisms underlying corticalization, we analyzed osteoblast-specific Osterix-knockout mice (Col-OMT). In control mice, corticalization was initiated after 7 postnatal days, and the number of osteoblasts in the peripheral spongiosa was increased compared to the number in the central spongiosa. In contrast, in Col-OMT mice, corticalization was delayed, and the number of osteoblasts in peripheral zones was unchanged compared to the central zone. Furthermore, femoral length was decreased in Col-OMT mice at 1 month. Because Col-OMT mice exhibited impaired matrix coalescence and osteoblast migration, we evaluated integrin signaling in Col-OMT mice. Osterix bound to the Itgb3 promoter and increased transcription of the Itgb3 gene in osteoblast cells. Interestingly, the inner and outer cortical bones were separated in Itgb3-null mice at postnatal day 7. In Itgb3-null mice, the number of osteoblasts in peripheral zones was not changed, and the femoral length was decreased. Taken together, these results indicate that Osterix regulates corticalization for longitudinal bone growth via the control of integrin β3 expression in osteoblasts. Our findings imply that the ability to control osteoblast function during corticalization may help in the treatment of short stature.
Highlights
The longitudinal growth of mammalian long bones is important in the determination of final body height and normal bone structure
Coalescence of trabecular bone was observed at postnatal day 7 (P7) (Fig. 2a), and trabecular bone had obviously coalesced into the metaphyseal cortex by P10 (Fig. 1)
This study showed that corticalization affecting longitudinal bone growth takes place at postnatal day 7 with the migration of osteoblasts to the peripheral spongiosa
Summary
The longitudinal growth of mammalian long bones is important in the determination of final body height and normal bone structure. The process of longitudinal bone growth is quite complex and is tightly regulated by several factors[1]. Trabecular bone is formed around calcified cartilage in the ossification zone in a process called endochondral bone formation[2,3,4,5]. The newly formed trabecular bone coalesces at the metaphyseal cortex. This event is called “corticalization” and is the process by which longitudinal bone growth is completed[6]. Corticalization is the last stage of longitudinal growth and plays an important role in completing the structure of adult bone, though the underlying genetic and molecular mechanisms of this process remain unknown
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