Effects of prostaglandin E2 and F2α on the skeleton of osteopenic ovariectomized rats

Ma, Yujie; Li, X.J.; Jee, Webster S. S.; McOsker, J.E.; Liang, Xiaoguang; Setterberg, R. B.; Chow, S. Y.

doi:10.1016/8756-3282(95)00387-8

Cited by 40 publications

(19 citation statements)

References 26 publications

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“…The involvement of LPA, which signals in part through Rho, is consistent with the role of RhoA and Rho-associated kinase in driving the differentiation of osteoblasts from mesenchymal stem cells [45]. Moreover, the dependence of osteogenesis on cyclooxygenase activity is in keeping with the well-established role of prostaglandins in stimulating bone formation [46] and in mediating skeletal mechanotransduction in vivo [47].…”

Section: Expression Of P2x7 In Cells Of the Osteoblast Lineagesupporting

confidence: 69%

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: Expression Of P2x7 In Cells Of the Osteoblast Lineagesupporting

confidence: 69%

Expression, signaling, and function of P2X7 receptors in bone

Grol

Panupinthu

Korcok

et al. 2009

Purinergic Signalling

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“…Several eicosanoids, including prostaglandin E 2 , stimulate bone formation (57) and have been implicated in skeletal mechanotransduction (58). In this regard, fluid shear stress increases PGE 2 release by calvarial osteoblasts from WT, but not P2X7 KO mice (8).…”

Section: Discussionmentioning

confidence: 99%

P2X7 Nucleotide Receptors Mediate Blebbing in Osteoblasts through a Pathway Involving Lysophosphatidic Acid

Panupinthu

Zhao

Possmayer

et al. 2007

Journal of Biological Chemistry

109

108

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Extracellular nucleotides, released in response to mechanical or inflammatory stimuli, signal through P2 receptors in many cell types, including osteoblasts. P2X7 receptors are ATP-gated cation channels that can induce formation of large membrane pores. Disruption of the gene encoding the P2X7 receptor leads to decreased periosteal bone formation and insensitivity of the skeleton to mechanical stimulation. Our purpose was to investigate signaling pathways coupled to P2X7 activation in osteoblasts. Live cell imaging showed that ATP or 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP), but not UTP, UDP, or 2-methylthio-ADP, induced dynamic membrane blebbing in calvarial osteoblasts. Blebbing was observed in calvarial cells from wildtype but not P2X7 knock-out mice. P2X7 receptors coupled to activation of phospholipase D and A 2 , inhibition of which suppressed BzATP-induced blebbing. Activation of these phospholipases leads to production of lysophosphatidic acid (LPA). LPA caused dynamic blebbing in osteoblasts from both wild-type and P2X7 knock-out mice, similar to that induced by BzATP in wildtype cells. However, LPA-induced blebbing was more rapid in onset and was not affected by inhibition of phospholipase D or A 2 . Blockade or desensitization of LPA receptors suppressed blebbing in response to LPA and BzATP, without affecting P2X7-stimulated pore formation. Thus, LPA functions downstream of P2X7 receptors to induce membrane blebbing. Furthermore, inhibition of Rho-associated kinase abolished blebbing induced by both BzATP and LPA. In summary, we propose a novel signaling axis that links P2X7 receptors through phospholipases to production of LPA and activation of Rho-associated kinase. This pathway may contribute to P2X7-stimulated osteogenesis during skeletal development and mechanotransduction.

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“…It is associated with diseases such as diabetes (4), osteoporosis (5,6), and menstrual disorder (7). However, it is mostly known for its effect on the female reproductive system.…”

mentioning

confidence: 99%

An Aldose Reductase with 20α-Hydroxysteroid Dehydrogenase Activity Is Most Likely the Enzyme Responsible for the Production of Prostaglandin F2α in the Bovine Endometrium

Madore¹,

Harvey

Parent

et al. 2003

Journal of Biological Chemistry

146

118

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Prostaglandins are important regulators of reproductive function. In particular, prostaglandin F2␣ (PGF 2␣ ) is involved in labor and is the functional mediator of luteolysis to initiate a new estrous cycle in many species. These actions have been extensively studied in ruminants, but the enzymes involved are not clearly identified. Our objective was to identify which prostaglandin F synthase is involved and to study its regulation in the endometrium and in endometrial primary cell cultures. The expression of all previously known prostaglandin F synthases (PGFSs), two newly discovered PGFS-like genes, and a 20␣-hydroxysteroid dehydrogenase was studied by Northern blot and reverse transcription PCR. These analyses revealed that none of the known PGFS or the PGFS-like genes were significantly expressed in the endometrium. On the other hand, the 20␣-hydroxysteroid dehydrogenase gene was strongly expressed in the endometrium at the time of luteolysis. The corresponding recombinant enzyme has a K m of 7 M for PGH 2 and a PGFS activity higher than the lung PGFS. This enzyme has two different activities with the ability to terminate the estrous cycle; it metabolizes progesterone and synthesizes PGF 2␣ . Taken together, these data point to this newly identified enzyme as the functional endometrial PGFS.Prostaglandins are local mediators acting through paracrine or autocrine mechanisms. Prostaglandins are produced from arachidonic acid liberated from phospholipid stores through the action of phospholipases. Arachidonic acid is then converted into prostaglandin H 2 (PGH 2 ), 1 the common precursor of all prostaglandins, through the cyclooxygenase and peroxydase activities of prostaglandin H synthase (PGHS). There are two PGHS: PGHS1 and PGHS2. These enzymes (also known as Cox-1 and Cox-2), which have been identified some 10 years ago, are still extensively studied. Because PGH 2 is the common precursor of all subtypes of prostaglandins and because these prostaglandin isotypes cause different and even opposing actions, the pathways leading to their individual formation need to be identified.Prostaglandin F2␣ (PGF 2␣ ) is involved in several physiological processes including pressure regulation in the eye (1), vasoconstriction (2), and renal filtration (3). It is associated with diseases such as diabetes (4), osteoporosis (5, 6), and menstrual disorder (7). However, it is mostly known for its effect on the female reproductive system. In mice, gene knockout of the FP receptor (the receptor for PGF 2␣ ) leads to a failure in the initiation of labor (8). For most mammalian species, the production of PGF 2␣ by the uterus is involved in the regulation of the ovarian cycle. This prostaglandin acts on the corpus luteum, initiating its regression (luteolysis) and leading to termination of the estrous cycle or of pregnancy (reviewed in Ref. 9). The regulation of PGF 2␣ production at the critical period of luteolysis or recognition of pregnancy has been studied extensively in ruminants. In cattle, PGF 2␣ is mainly synthesized by epit...

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Effects of prostaglandin E2 and F2α on the skeleton of osteopenic ovariectomized rats

Cited by 40 publications

References 26 publications

Expression, signaling, and function of P2X7 receptors in bone

Expression, signaling, and function of P2X7 receptors in bone

P2X7 Nucleotide Receptors Mediate Blebbing in Osteoblasts through a Pathway Involving Lysophosphatidic Acid

An Aldose Reductase with 20α-Hydroxysteroid Dehydrogenase Activity Is Most Likely the Enzyme Responsible for the Production of Prostaglandin F2α in the Bovine Endometrium

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