Vascular Invasion of Epiphyseal Growth Plate in Osteopetrotic (op/op) Mouse Tibiae

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To clarify what type of cells lead vascular invasion of epiphyseal growth plate in developing long bones, we conducted immunohistochemical and electron microscopic studies on the op/op mouse tibia which has an inheriting deficiency of macrophages and osteoclasts. Despite an absence of both TRAP-positive osteoclasts and F4/80-positive macrophages, resorption of epiphyseal cartilage followed by vascular invasion was evident in op/op mouse tibiae. Electron microscopic observation revealed that cells subjacent to the lowermost hypertrophic chondrocyte lacunae were almost exclusively vascular endothelial cells. Immunohistochemically, both cellular elements and extracellular matrix at the vascular invasion front of op/op mouse epiphysis were strongly positive for MMP-9. In situ hybridization revealed a distinct localization of mRNA for MMP-9 in cells located at the same region. From these findings, we hypothesize that vascular endothelial cells themselves are primarily responsible for resorbing the transverse septa of hypertrophic chondrocytes lacunae, and neither osteoclasts nor macrophages involve in this process.
硬組織再生生物学会の論文