The primary function of gp130 signaling in osteoblasts is to maintain bone formation and strength, rather than promote osteoclast formation

J Bone Miner Res. 2014 Jun;29(6):1492-505. doi: 10.1002/jbmr.2159.


Interleukin-6 (IL-6) family cytokines act via gp130 in the osteoblast lineage to stimulate the formation of osteoclasts (bone resorbing cells) and the activity of osteoblasts (bone forming cells), and to inhibit expression of the osteocyte protein, sclerostin. We report here that a profound reduction in trabecular bone mass occurs both when gp130 is deleted in the entire osteoblast lineage (Osx1Cre gp130 f/f) and when this deletion is restricted to osteocytes (DMP1Cre gp130 f/f). This was caused not by an alteration in osteoclastogenesis, but by a low level of bone formation specific to the trabecular compartment. In contrast, cortical diameter increased to maintain ultimate bone strength, despite a reduction in collagen type 1 production. We conclude that osteocytic gp130 signaling is required for normal trabecular bone mass and proper cortical bone composition.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Bone and Bones / anatomy & histology
  • Bone and Bones / metabolism
  • Cell Count
  • Cell Lineage
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Cytokine Receptor gp130 / metabolism*
  • Female
  • Gene Deletion
  • Gene Knockdown Techniques
  • Glycoproteins / metabolism
  • Integrases / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Organ Size
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Osteocytes / metabolism
  • Osteogenesis*
  • Reproducibility of Results
  • Signal Transduction*
  • Sp7 Transcription Factor
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Adaptor Proteins, Signal Transducing
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Glycoproteins
  • Il6st protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Sost protein, mouse
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Transcription Factors
  • Osteocalcin
  • Cytokine Receptor gp130
  • Cre recombinase
  • Integrases