Accelerated Cartilage Resorption by Chondroclasts during Bone Fracture Healing in Osteoprotegerin-Deficient Mice
| Autor: | Hisataka Yasuda, Tokuhiro Kimura, Hiroshi Kawaguchi, Norikazu Ota, Masaki Yoda, Kazuhiro Chiba, Morio Matsumoto, Hironari Takaishi, Takahide Tohmonda, Hiroyasu Ikegami, Jiro Takito, Naoto Kosaki, Yoshiaki Toyama, Yasunori Okada |
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| Rok vydání: | 2009 |
| Předmět: |
Male
musculoskeletal diseases medicine.medical_specialty Bone healing Cell Line Fractures Bone Mice Chondrocytes Endocrinology Osteoprotegerin Internal medicine Bone cell medicine Animals Endochondral ossification Cells Cultured Fracture Healing Mice Knockout biology Chemistry Ossification Cartilage RANK Ligand Resorption Mice Inbred C57BL medicine.anatomical_structure RANKL biology.protein Female medicine.symptom |
| Zdroj: | Endocrinology. 150:4823-4834 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2009-0452 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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