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Matrix-embedded cells control osteoclast formation.

Nature medicine | 2011

Osteoclasts resorb the mineralized matrices formed by chondrocytes or osteoblasts. The cytokine receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and thought to be supplied by osteoblasts or their precursors, thereby linking bone formation to resorption. However, RANKL is expressed by a variety of cell types, and it is unclear which of them are essential sources for osteoclast formation. Here we have used a mouse strain in which RANKL can be conditionally deleted and a series of Cre-deleter strains to demonstrate that hypertrophic chondrocytes and osteocytes, both of which are embedded in matrix, are essential sources of the RANKL that controls mineralized cartilage resorption and bone remodeling, respectively. Moreover, osteocyte RANKL is responsible for the bone loss associated with unloading. Contrary to the current paradigm, RANKL produced by osteoblasts or their progenitors does not contribute to adult bone remodeling. These results suggest that the rate-limiting step of matrix resorption is controlled by cells embedded within the matrix itself.

Pubmed ID: 21909103 RIS Download

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: AG13918
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR049794
  • Agency: NIAMS NIH HHS, United States
    Id: AR049794
  • Agency: NIA NIH HHS, United States
    Id: P01 AG013918
  • Agency: BLRD VA, United States
    Id: I01 BX000294
  • Agency: NCRR NIH HHS, United States
    Id: 1UL1RR029884
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR049794-09

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B6N.FVB-Tg(Dmp1-cre)1Jqfe/BwdJ (tool)

RRID:IMSR_JAX:023047

Mus musculus with name B6N.FVB-Tg(Dmp1-cre)1Jqfe/BwdJ from IMSR.

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