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

Research output: Contribution to journalArticle

26 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

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Osteoprotegerin
Fracture Healing
Bone Fractures
Chondrocytes
Cartilage
Bone and Bones
RANK Ligand
Parathyroid Hormone-Related Protein
Calcitriol
Bony Callus
Osteoclasts
Bone Resorption
Cytoplasmic and Nuclear Receptors
Interleukin-1
Osteogenesis
Capsules
Spleen
Kidney

ASJC Scopus subject areas

  • Endocrinology

Cite this

Ota, N., Takaishi, H., Kosaki, N., Takito, J., Yoda, M., Tohmonda, T., ... 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

Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice. / Ota, Norikazu; Takaishi, Hironari; Kosaki, Naoto; Takito, Jiro; Yoda, Masaki; Tohmonda, Takahide; Kimura, Tokuhiro; Okada, Yasunori; Yasuda, Hisataka; Kawaguchi, Hiroshi; Matsumoto, Morio; Chiba, Kazuhiro; Ikegami, Hiroyasu; Toyama, Yoshiaki.

In: Endocrinology, Vol. 150, No. 11, 11.2009, p. 4823-4834.

Research output: Contribution to journalArticle

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, vol. 150, no. 11, pp. 4823-4834. https://doi.org/10.1210/en.2009-0452
Ota, Norikazu ; Takaishi, Hironari ; Kosaki, Naoto ; Takito, Jiro ; Yoda, Masaki ; Tohmonda, Takahide ; Kimura, Tokuhiro ; Okada, Yasunori ; Yasuda, Hisataka ; Kawaguchi, Hiroshi ; Matsumoto, Morio ; Chiba, Kazuhiro ; Ikegami, Hiroyasu ; Toyama, Yoshiaki. / Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice. In: Endocrinology. 2009 ; Vol. 150, No. 11. pp. 4823-4834.
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