Erschienen in:
Open Access
01.12.2012 | Poster presentation
Activation of TRPV4 promotes osteoclasts differentiation
verfasst von:
Ritsuko Masuyama
Erschienen in:
Arthritis Research & Therapy
|
Sonderheft 1/2012
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Excerpt
Osteoclast differentiation is critically dependent on cellular calcium (Ca
2+) signaling. Intracellular Ca
2+ concentration ([Ca
2+]
i) is regulated by two flux pathways; Ca
2+ oscillations evoked by the release of Ca
2+ from the endoplasmic reticulum, and/or Ca
2+ entry from the extracellular fluid. The latter is carried out by the plasmamembrane localized Ca
2+ permeable channel such as "transient receptor potentials (Trps)". Trpv4-deficient mice show an increased bone mass due to impaired osteoclast maturation, because Trpv4 mediates Ca
2+ influx at the late stage of osteoclast differentiation and hereby regulates Ca
2+ signaling [
1]. Furthermore, substitutions of amino acids R616Q/V620I of Trpv4 have been discovered as gain of function mutations resulting in increased Ca
2+ transport [
2]. Since the region of these substitutions at the trans-membrane pore domain is perfectly conserved between species, we created a mutant of the mouse Trpv4 (Trpv4
R616Q/V620I) and characterized it on Ca
2+ signaling especially in the occurrences of oscillations at the initial step of osteoclast differentiation. …