Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice

Norikazu Ota, Hironari Takaishi, Naoto Kosaki, Jiro Takito, Masaki Yoda, Takahide Tohmonda, Tokuhiro Kimura, Yasunori Okada, Hisataka Yasuda, Hiroshi Kawaguchi, Morio Matsumoto, Kazuhiro Chiba, Hiroyasu Ikegami, Yoshiaki Toyama

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28 Citations (Scopus)

Abstract

Receptor activator of nuclear factor-κB 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 D3, PTHrP, IL-1α, and TNF-α. Thus, local OPG produced by chondrocytes probably controls cartilage resorption as a negative regulator for chondrocyte-dependent chondroclastogenesis.

Original languageEnglish
Pages (from-to)4823-4834
Number of pages12
JournalEndocrinology
Volume150
Issue number11
DOIs
Publication statusPublished - 2009 Nov

ASJC Scopus subject areas

  • Endocrinology

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    Ota, N., Takaishi, H., Kosaki, N., Takito, J., Yoda, M., Tohmonda, T., Kimura, T., Okada, Y., Yasuda, H., Kawaguchi, H., Matsumoto, M., Chiba, K., Ikegami, H., & Toyama, Y. (2009). Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice. Endocrinology, 150(11), 4823-4834. https://doi.org/10.1210/en.2009-0452