Purinergic signalling in osteoblasts

Gartland, Alison; Orriss, Isabel R.; Rumney, Robin M. H.; Bond, Alistair P.; Arnett, Timothy R.; Gallagher, James A.

doi:10.2741/3912

Cited by 35 publications

(33 citation statements)

References 88 publications

(106 reference statements)

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“…Entpd5 encodes a secreted ectonucleoside triphosphate/diphosphohydrolase that preferably hydrolyzes extracellular nucleotide diphosphates (21,22) into nucleotide monophosphates and inorganic phosphate. Circulating extracellular nucleotides are known to be important purinergic signaling molecules that can generate a variety of physiological responses (25,26). Although we do not exclude the possibility of an additional role of purinergic signaling in skeletal mineralization (26), our data rather point to a role of Entpd5 in phosphate homeostasis.…”

Section: Discussionmentioning

confidence: 50%

“…Circulating extracellular nucleotides are known to be important purinergic signaling molecules that can generate a variety of physiological responses (25,26). Although we do not exclude the possibility of an additional role of purinergic signaling in skeletal mineralization (26), our data rather point to a role of Entpd5 in phosphate homeostasis.…”

Section: Discussionmentioning

confidence: 50%

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Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish

Huitema

Apschner

Logister

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Bone mineralization is an essential step during the embryonic development of vertebrates, and bone serves vital functions in human physiology. To systematically identify unique gene functions essential for osteogenesis, we performed a forward genetic screen in zebrafish and isolated a mutant, no bone (nob), that does not form any mineralized bone. Positional cloning of nob identified the causative gene to encode ectonucleoside triphosphate/ diphosphohydrolase 5 (entpd5); analysis of its expression pattern demonstrates that entpd5 is specifically expressed in osteoblasts. An additional mutant, dragonfish (dgf), exhibits ectopic mineralization in the craniofacial and axial skeleton and encodes a loss-offunction allele of ectonucleotide pyrophosphatase phosphodiesterase 1 (enpp1). Intriguingly, generation of double-mutant nob/ dgf embryos restored skeletal mineralization in nob mutants, indicating that mechanistically, Entpd5 and Enpp1 act as reciprocal regulators of phosphate/pyrophosphate homeostasis in vivo. Consistent with this, entpd5 mutant embryos can be rescued by high levels of inorganic phosphate, and phosphate-regulating factors, such as fgf23 and npt2a, are significantly affected in entpd5 mutant embryos. Our study demonstrates that Entpd5 represents a previously unappreciated essential player in phosphate homeostasis and skeletal mineralization.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 50%

Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish

Huitema

Apschner

Logister

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Studies using primary rat and mouse calvarial osteoblasts, human osteoblast-like cell lines (MG-63, OHS-4, SaM-1, SaOS-2, Te85) and rat osteosarcoma cell lines (UMR106-01, ROS17/2,8) have all described expression of most or all P2X and P2Y receptor subtypes in osteoblasts (see reviews (Burnstock et al, 2013;Gartland et al, 2012a)). P2 receptor mediated signalling has now been shown to exert many effects on osteoblast proliferation, differentiation, function, gene expression and cell signalling.…”

Section: The Role Of Purinergic Signalling In Osteoblast Biologymentioning

confidence: 99%

The role of purinergic signalling in the musculoskeletal system

Orriss

2015

Autonomic Neuroscience

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“…Whereas the role of ATP in bone metabolism [1,2] has been revealed to some extent and quite a few papers have been published in this respect, functions of its metabolite adenosine are not understood. Bone remodelling is a continuous, life-long process that maintains skeletal integrity.…”

Section: Introductory Note By the Associate Editormentioning

confidence: 99%

Does adenosine play a role in bone formation, resorption and repair?

Evans

2012

Purinergic Signalling

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There has been increasing interest recently in the role purinergic signalling in the physiology and pathophysiology of musculoskeletal tissues, especially bone. Whereas the role of ATP in bone metabolism [1,2] has been revealed to some extent and quite a few papers have been published in this respect, functions of its metabolite adenosine are not understood. Bone remodelling is a continuous, life-long process that maintains skeletal integrity. It is orchestrated by the three bone cell types (osteoblasts, osteoclasts and osteocytes), and impairments eventually result in diseases such as osteoporosis. Although there is much insight into the systems that maintain healthy bone, there is still a need to develop new therapies. The hypothesis that the adenosine signalling pathways might provide new targets for bone disease has gained further momentum recently with the publication of the following two papers that are commented on by Bronwen A. J. Evans of Cardiff University. Interestingly enough, the first article deals with findings obtained using CD73 null mice, that have also been the subject of another recently published Highlight [3] that focused on the role of local and systemic adenosine in modulation of antitumour responses in vivo. Here, CD73 null mice have been exploited to unveil a potential role of adenosine in osteoblast differentiation. In the second commented article, by using adenosine A2B receptor knockout mice, this receptor is identified as a main target for adenosine in promoting the differentiation of mesenchymal stem cell to osteoblasts. Article summaryM. Takedachi and colleagues hypothesized that CD73 may be involved in regulating function of the bone forming cell (osteoblast) through modulating nucleotide metabolism and generating extracellular adenosine that can activate adenosine receptors (ARs). To address this hypothesis, they asked whether CD73 functionally regulates bone metabolism in vivo by characterizing the bone phenotype of cd73−/− mice. In addition, they investigated the involvement of CD73 and AR signalling in osteoblast differentiation in vitro.Micro-computed tomography (μCT) showed that 13 week old male mice had osteopenia, and that this was due to reduced trabecular bone volume, decreased trabecular number and thickness, and increased trabecular separation in cd73−/− mice when compared to wild-type controls. Subsequent work measuring biochemical markers of bone formation showed that osteocalcin (bone formation marker) was decreased in cd73−/− mice whereas bone resorption markers (TRAP5b and fragments of type I collagen) were comparable to wild-type animals. The association of the osteoblast to the impared bone phenotype seen in cd73−/− mice was further substantiated using quantitative RT-PCR. These

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Purinergic signalling in osteoblasts

Cited by 35 publications

References 88 publications

Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish

Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish

The role of purinergic signalling in the musculoskeletal system

Does adenosine play a role in bone formation, resorption and repair?

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