Coupling Factors: How Many Candidates Can There Be?

Martın, Thomas

doi:10.1002/jbmr.2276

Cited by 13 publications

(11 citation statements)

References 35 publications

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“…This suggests a deficiency in the coupling factor activity from gp130-deficient osteoclasts required for remodelling and consolidation of the trabecular network during early adulthood. Factors that contribute to coupling may be secreted by osteoclasts or released by the bone matrix, and may either stimulate or inhibit bone formation [42][43][44][45]. Since resorptive activity of Ctsk.gp130 f/f osteoclasts was not reduced in vivo, the coupling activity responsible for the reduced bone formation on trabecular bone surfaces in these mice is unlikely to be one released from the bone matrix.…”

Section: Discussionmentioning

confidence: 87%

“…This activity is attributed to the release of activities that couple the resorptive activation of osteoclasts with subsequent bone formation by osteoblasts during remodelling in the "Basic Multicellular Unit" (BMU), and thereby maintain bone mass. Such "coupling" factors are either produced by the osteoclasts themselves, or released during resorption of the bone matrix, and many have been proposed to date [42][43][44][45]. Here we report that CtskCre-directed genetic deletion of gp130 in osteoclasts is capable of separating the osteoclast's resorptive function from its coupling activity.…”

Section: Discussionmentioning

confidence: 92%

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Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone

Johnson

McGregor

Brennan

et al. 2015

Bone

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 92%

Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone

Johnson

McGregor

Brennan

et al. 2015

Bone

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“…This coordinated action of osteoclasts and osteoblasts is essential for normal skeletal remodeling, and the consequent bone renewal and maintenance of bone mass. Therefore, signals that govern the fate and function of cells of the osteoblast and osteoclast lineages, and signals that coordinate the actions of these cells are of the essence for normal bone remodeling [5, 6]. …”

Section: Introductionmentioning

confidence: 99%

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations

Canalis

Zanotti

2016

Curr Osteoporos Rep

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Notch plays an important function in skeletal homeostasis, osteoblastogenesis and osteoclastogenesis. Hajdu Cheney syndrome (HCS) is a rare disease associated with mutations in NOTCH2 leading to the translation of a truncated NOTCH2 stable protein. As a consequence, a gain-of-NOTCH2 function is manifested. HCS is inherited as an autosomal dominant disease although sporadic cases exist. HCS is characterized by craniofacial developmental defects, including platybasia and wormian bones, osteoporosis with fractures and acroosteolysis. Subjects may suffer severe neurological complications, and HCS presents with cardiovascular defects and polycystic kidneys. An experimental mouse model harboring a HCSNotch2 mutation exhibits osteopenia secondary to enhanced bone resorption suggesting this as a possible mechanism for the skeletal disease. If the same mechanisms were operational in humans, anti-resorptive therapy could correct the bone loss, but not necessarily the acroosteolysis. In conclusion, HCS is a devastating disease associated with a gain-of-NOTCH2 function resulting in diverse clinical manifestations.

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“…Bone remodeling consists in the coordinated resorption and formation of bone, a process that requires the integrated involvement of cells of the osteoclast and osteoblast lineage and of signals released by these cells [ 43 - 48 ]. Osteoclasts are multinucleated cells derived from the fusion of mononuclear precursors of the hematopoietic lineage.…”

Section: Reviewmentioning

confidence: 99%

Hajdu-Cheney syndrome: a review

Canalis

Zanotti

2014

Orphanet J Rare Dis

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Hajdu Cheney Syndrome (HCS), Orpha 955, is a rare disease characterized by acroosteolysis, severe osteoporosis, short stature, specific craniofacial features, wormian bones, neurological symptoms, cardiovascular defects and polycystic kidneys. HCS is rare and is inherited as autosomal dominant although many sporadic cases have been reported. HCS is associated with mutations in exon 34 of NOTCH2 upstream the PEST domain that lead to the creation of a truncated and stable NOTCH2 protein with enhanced NOTCH2 signaling activity. Although the number of cases with NOTCH2 mutations reported are limited, it would seem that the diagnosis of HCS can be established by sequence analysis of exon 34 of NOTCH2. Notch receptors are single-pass transmembrane proteins that determine cell fate, and play a critical role in skeletal development and homeostasis. Dysregulation of Notch signaling is associated with skeletal developmental disorders. There is limited information about the mechanisms of the bone loss and acroosteolysis in HCS making decisions regarding therapeutic intervention difficult. Bone antiresorptive and anabolic agents have been tried to treat the osteoporosis, but their benefit has not been established. In conclusion, Notch regulates skeletal development and bone remodeling, and gain-of-function mutations of NOTCH2 are associated with HCS.

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Coupling Factors: How Many Candidates Can There Be?

Cited by 13 publications

References 35 publications

Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone

Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations

Hajdu-Cheney syndrome: a review

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