Single nucleotide polymorphisms in the P2X7 gene are associated to fracture risk and to effect of estrogen treatment

Ohlendorff, Stine; Tofteng, Charlotte Landbo; Jensen, Jens–Erik Beck; Petersen, Solveig; Civitelli, Roberto; Fenger, Mogens; Abrahamsen, Bo; Hermann, Anne Pernille; Eiken, Patrick W.; Jørgensen, Niklas Rye

doi:10.1097/fpc.0b013e3280951625

Cited by 96 publications

(113 citation statements)

References 34 publications

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“…As well, impaired osteoblast differentiation and bone formation may contribute to increased fracture risk. It is worth noting that the skeletal changes observed in postmenopausal women with loss-of-function polymorphisms of the P2X7 receptor [79] correspond to the phenotypic changes in the P2rx7 −/− mouse described by Ke et al [25].…”

Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 54%

“…Moreover, the Glu496Ala polymorphism resulted in decreased susceptibility to ATP-induced death of osteoclastlike cells derived from peripheral blood monocytes. Increased skeletal fragility in patients with loss-of-function polymorphisms in the P2X7 receptor is consistent with decreased susceptibility of osteoclasts to apoptosis [79]. As well, impaired osteoblast differentiation and bone formation may contribute to increased fracture risk.…”

Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 75%

“…Under such conditions, wild-type osteoclasts were more susceptible to apoptosis and showed lower survival rates than did osteoclasts isolated from P2rx7 −/− mice. A more recent study provided further evidence for a role of the P2X7 receptor in mediating apoptosis of osteoclasts [79] (see below).…”

Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 84%

“…The relatively common Glu496Ala polymorphism results in reduced pore-forming ability [82] without altering channel function [87], whereas the Ile568Asn polymorphism prevents normal channel trafficking and function [88]. In this regard, Ohlendorff et al found that Glu496Ala and Ile568Asn single-nucleotide polymorphisms in the human P2X7 receptor are associated with 10-year fracture risk in postmenopausal women [79]. Moreover, the Glu496Ala polymorphism resulted in decreased susceptibility to ATP-induced death of osteoclastlike cells derived from peripheral blood monocytes.…”

Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 99%

“…The P2rx7 −/− mouse described by Ke et al exhibits decreased periosteal bone formation, increased trabecular bone resorption [25], and impaired response to mechanical stimulation [26]. Moreover, P2X7 receptor activation in osteoblasts enhances differentiation and bone formation [33], whereas its activation in osteoclasts results in apoptosis [52,62,79] (Fig. 10).…”

Section: Prospects and Conclusionmentioning

confidence: 99%

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Expression, signaling, and function of P2X7 receptors in bone

Grol

Panupinthu

Korcok

et al. 2009

Purinergic Signalling

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Nucleotides released from cells in response to mechanical stimulation or injury may serve as paracrine regulators of bone cell function. Extracellular nucleotides bind to multiple subtypes of P2 receptors on osteoblasts (the cells responsible for bone formation) and osteoclasts (cells with the unique ability to resorb mineralized tissues). Both cell lineages express the P2X7 receptor subtype. The skeletal phenotype of mice with targeted disruption of P2rx7 points to interesting roles for this receptor in the regulation of bone formation and resorption, as well as the response of the skeleton to mechanical stimulation. This paper reviews recent work on the expression of P2X7 receptors in bone, their associated signal transduction mechanisms and roles in regulating bone formation and resorption. Areas for future research in this field are also discussed.

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Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 54%

Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 75%

Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 84%

Section: Physiological Function Of P2x7 Receptors In Osteoclastsmentioning

confidence: 99%

Section: Prospects and Conclusionmentioning

confidence: 99%

See 3 more Smart Citations

Expression, signaling, and function of P2X7 receptors in bone

Grol

Panupinthu

Korcok

et al. 2009

Purinergic Signalling

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Systemic and psychiatric disorders associated with polymorphisms of the P2RX7 gene

Kapoor¹

2008

American J of Med Genetics Pt B

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Tension Force‐Induced ATP Promotes Osteogenesis Through P2X7 Receptor in Osteoblasts

Kariya

Tanabe²,

Shionome³

et al. 2014

J of Cellular Biochemistry

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Orthodontic tooth movement induces alveolar bone resorption and formation by mechanical stimuli. Force exerted on the traction side promotes bone formation. Adenosine triphosphate (ATP) is one of the key mediators that respond to bone cells by mechanical stimuli. However, the effect of tension force (TF)-induced ATP on osteogenesis is inadequately understood. Accordingly, we investigated the effect of TF on ATP production and osteogenesis in MC3T3-E1 cells. Cells were incubated in the presence or absence of P2X7 receptor antagonist A438079, and then stimulated with or without cyclic TF (6% or 18%) for a maximum of 24 h using Flexercell Strain Unit 3000. TF significantly increased extracellular ATP release compared to control. Six percent TF had maximum effect on ATP release compared to 18% TF and control. Six percent TF induced the expression of Runx2 and Osterix. Six percent TF also increased the expression of extracellular matrix proteins (ECMPs), ALP activity, and the calcium content in ECM. A438079 blocked the stimulatory effect of 6% TF on the expression of Runx2, Osterix and ECMPs, ALP activity, and calcium content in ECM. This study indicated that TF-induced extracellular ATP is released in osteoblasts, suggesting that TF-induced ATP promotes osteogenesis by autocrine action through P2X7 receptor in osteoblasts. J. Cell. Biochem. 116: 12–21, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.

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Single nucleotide polymorphisms in the P2X7 gene are associated to fracture risk and to effect of estrogen treatment

Cited by 96 publications

References 34 publications

Expression, signaling, and function of P2X7 receptors in bone

Expression, signaling, and function of P2X7 receptors in bone

Systemic and psychiatric disorders associated with polymorphisms of the P2RX7 gene

Tension Force‐Induced ATP Promotes Osteogenesis Through P2X7 Receptor in Osteoblasts

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