title: Hypertrophic chondrocytes in the rabbit growth plate can proliferate and differentiate into osteogenic cells when capillary invasion is interposed by a membrane filter.
abstract: The fate of hypertrophic chondrocytes during endochondral ossification remains controversial. It has long been thought that the calcified cartilage is invaded by blood vessels and that new bone is deposited on the surface of the eroded cartilage by newly arrived cells. The present study was designed to determine whether hypertrophic chondrocytes were destined to die or could survive to participate in new bone formation. In a rabbit experiment, a membrane filter with a pore size of 1 µm was inserted in the middle of the hypertrophic zone of the distal growth plate of ulna. In 33 of 37 animals, vascular invasion was successfully interposed by the membrane filter. During 8 days, the cartilage growth plate was enlarged, making the thickness 3-fold greater than that of the nonoperated control side. Histological examination demonstrated that the hypertrophic zone was exclusively elongated. At the terminal end of the growth plate, hypertrophic chondrocytes extruded from their territorial matrix into the open cavity on the surface of the membrane filter. The progenies of hypertrophic chondrocytes (PHCs) were PCNA positive and caspase-3 negative. In situ hybridization studies demonstrated that PHCs did not express cartilage matrix proteins anymore but expressed bone matrix proteins. Immunohistochemical studies also demonstrated that the new matrix produced by PHCs contained type I collagen, osteonectin, and osteocalcin. Based on these results, we concluded that hypertrophic chondrocytes switched into bone-forming cells after vascular invasion was interposed in the normal growth plate.
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Enishi
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Yukata
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Sato
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sairyo
authors.affiliation: Department of Orthopedics, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yasui
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology; D002196:Capillaries / Q000378:metabolism / Q000502:physiology*; D002356:Cartilage / Q000378:metabolism / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism / Q000502:physiology*; D006984:Hypertrophy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D015676:Osteonectin / Q000378:metabolism; D011817:Rabbits
chemical_list: D024042:Collagen Type I; D015676:Osteonectin; D015675:Osteocalcin; D053148:Caspase 3