Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice.
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.
Ota
Norikazu
N
Department of Orthopaedic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Takaishi
Hironari
H
Kosaki
Naoto
N
Takito
Jiro
J
Yoda
Masaki
M
Tohmonda
Takahide
T
Kimura
Tokuhiro
T
Okada
Yasunori
Y
Yasuda
Hisataka
H
Kawaguchi
Hiroshi
H
Matsumoto
Morio
M
Chiba
Kazuhiro
K
Ikegami
Hiroyasu
H
Toyama
Yoshiaki
Y
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
D053244:Osteoprotegerin; D053245:RANK Ligand