Ciliary Neurotrophic Factor Inhibits Bone Formation and Plays a Sex-Specific Role in Bone Growth and Remodeling

  title={Ciliary Neurotrophic Factor Inhibits Bone Formation and Plays a Sex-Specific Role in Bone Growth and Remodeling},
  author={Narelle E. McGregor and Ingrid J. Poulton and Emma C. Walker and Sueli Pompolo and Julian M W Quinn and T John Martin and Natalie A. Sims},
  journal={Calcified Tissue International},
Ciliary neurotrophic factor (CNTF) receptor (CNTFR) expression has been described in osteoblast-like cells, suggesting a role for CNTF in bone metabolism. When bound to CNTF, neuropoietin (NP), or cardiotrophin-like-cytokine (CLC), CNTFR forms a signaling complex with gp130 and the leukemia inhibitory factor receptor, which both play critical roles in bone cell biology. This study aimed to determine the role of CNTFR-signaling cytokines in bone. Immunohistochemistry detected CNTF in osteoblasts… 
Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure
The data reveal that haematopoietic cell-derived CNTF has roles in regulating BM B cell lymphopoiesis and both trabecular and cortical bone, the latter in a sex-dependent manner.
The Primary Function of gp130 Signaling in Osteoblasts Is To Maintain Bone Formation and Strength, Rather Than Promote Osteoclast Formation
It is concluded that osteocytic gp130 signaling is required for normal trabecular bone mass and proper cortical bone composition and cortical diameter increased to maintain ultimate bone strength, despite a reduction in collagen type 1 production.
GP130 cytokines and bone remodelling in health and disease.
The current models of paracrine and endocrine actions of gp130-signalling cytokines inBone remodelling and growth, as well as their impact in pathologic bone remodelling evident in periodontal disease, rheumatoid arthritis, spondylarthropathies and osteoarthritis are discussed.
Contrasting roles of leukemia inhibitory factor in murine bone development and remodeling involve region‐specific changes in vascularization
In adult bone undergoing remodeling osteoclast formation was unaffected by LIF deficiency, whereas osteoblast formation and function were both significantly impaired, resulting in osteopenia, whereas an anatomically separate LIF‐dependent pathway regulates osteobasts and adipocyte commitment in bone remodeling.
Leukemia inhibitory factor: A paracrine mediator of bone metabolism
The expression patterns of Lif and LIFR in bone, their regulation by physiological and inflammatory agents, as well as cell-specific influences of LIF on osteoblast, osteoclast, chondrocyte, and adipocyte differentiation are described.


Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice.
What is believed to be a novel pathway by which bone formation can be stimulated independently of bone resorption is revealed and new insights into OSMR and LIFR signaling are provided that are relevant to other medical conditions, including cardiovascular and neurodegenerative diseases and cancer.
Cardiotrophin‐1 Is an Osteoclast‐Derived Stimulus of Bone Formation Required for Normal Bone Remodeling
CT‐1 may now be classed as an essential osteoclast‐derived stimulus of both bone formation and resorption.
Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways.
GP130 is essential for normal bone growth and trabecular bone mass, with balanced regulation depending on selective activation of STAT1/3 and SHP2/ras/MAPK, respectively, the latter pathway can directly inhibit osteoclastogenesis in vivo.
Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist
It is shown here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483) and its unique localization and action on osteoblasts suggest that sclerost in may be the previously proposed osteocyte-derived factor that is transported to osteoblast at the bone surface and inhibits bone formation.
gp130 signaling in bone cell biology: Multiple roles revealed by analysis of genetically altered mice
  • N. Sims
  • Biology
    Molecular and Cellular Endocrinology
  • 2009
Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5.
IGF-I treatment almost completely rescued all effects of the GHR(-/-) on both bone growth and remodeling, supporting a direct effect of IGF-I on both osteoblasts and chondrocytes.
Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone.
These findings identify the PPR as a crucial mediator of both bone-forming and bone-resorbing actions of PTH, and underline the complexity and heterogeneity of the osteoblast population and/or their regulatory microenvironment.
Gp130-mediated signaling is necessary for normal osteoblastic function in vivo and in vitro.
The importance of gp130 signaling for osteoblast function and calcium homeostasis is demonstrated, as well as the ability of osteoblastic cells from gp130(-/-) mice to stimulate osteoclastogenesis from normal precursors in vitro or to increase receptor activator of nuclear factor-kappa B ligand mRNA levels after exposure to PTH.
Osteoclasts are present in gp130-deficient mice.
The results suggest that the formation of osteoclasts is not solely dependent on gp130 signaling, at least during fetal development, and the osteoclastic bone resorption in gp130-deficient mice may be caused by the functional redundancy of bone-resorbing hormones and cytokines other than those of the IL-6 family.
Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling.
A role for the perinatal T surge in determining adult bone length and adult circulating T determines adult bone density is suggested and confirmed.