title: Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice.
abstract: Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG), a decoy receptor of RANKL, maintain bone mass by regulating the differentiation of osteoclasts, which are bone-resorbing cells. Endochondral bone ossification and bone fracture healing involve cartilage resorption, a less well-understood process that is needed for replacement of cartilage by bone. Here we describe the role of OPG produced by chondrocytes in chondroclastogenesis. Fracture healing in OPG(-/-) mice showed faster union of the fractured bone, faster resorption of the cartilaginous callus, and an increased number of chondroclasts at the chondroosseous junctions compared with that in wild-type littermates. When a cultured pellet of OPG(-/-) chondrocytes was transplanted beneath the kidney capsule, the pellet recruited many chondroclasts. The pellet showed the ability to induce tartrate-resistant acid phosphatase-positive multinucleated cells from RAW 264.7 cells in vitro. Finally, OPG(-/-) chondrocytes (but not wild-type chondrocytes) cultured with spleen cells induced many tartrate-resistant acid phosphatase-positive multinucleated cells. The expression of RANKL and OPG in chondrocytes was regulated by several osteotropic factors including 1,25-dihydroxyvitamin D(3), PTHrP, IL-1alpha, and TNF-alpha. Thus, local OPG produced by chondrocytes probably controls cartilage resorption as a negative regulator for chondrocyte-dependent chondroclastogenesis.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ota
authors.forename: Hironari
authors.initials: H
authors.lastname: Takaishi
authors.forename: Naoto
authors.initials: N
authors.lastname: Kosaki
authors.forename: Jiro
authors.initials: J
authors.lastname: Takito
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoda
authors.forename: Takahide
authors.initials: T
authors.lastname: Tohmonda
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ikegami
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
mesh_terms: D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D002460:Cell Line; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D005260:Female; D017102:Fracture Healing; D050723:Fractures, Bone / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053244:Osteoprotegerin / Q000172:deficiency* / Q000235:genetics; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand