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

Rachelle W Johnson; Holly J Brennan; Christina Vrahnas; Ingrid J Poulton; Narelle E McGregor; Therese Standal; Emma C Walker; Thuan-Tzen Koh; Huynh Nguyen; Nicole C Walsh; Mark R Forwood; T John Martin; Natalie A Sims

doi:10.1002/jbmr.2159

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.

Authors

Rachelle W Johnson¹, Holly J Brennan, Christina Vrahnas, Ingrid J Poulton, Narelle E McGregor, Therese Standal, Emma C Walker, Thuan-Tzen Koh, Huynh Nguyen, Nicole C Walsh, Mark R Forwood, T John Martin, Natalie A Sims

Affiliation

¹ St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.

PMID: 24339143
DOI: 10.1002/jbmr.2159

Abstract

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.

Keywords: BONE MATRIX; CELL/TISSUE SIGNALING; CYTOKINES; ENDOCRINE PATHWAYS; MATRIX MINERALIZATION; OSTEOBLASTS.

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

Substances

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