Investigation of the Relationship of Acid-Sensing Ion Channels and Osteoblasts

A stable physiologic systemic pH is critical for the survival of mammals. Homeostasis of the intracellular hydrogen ion concentration is pivotal to the maintenance of cell function and viability, but pH fluctuations are present in both intracellular and extracellular compartments in normal physiological and pathophysiological conditions. Bone cells, including osteoblasts and osteoclasts, respond to pH changes in the physiological range, but the sensor(s) that can mediate these pH changes are largely unknown. Acid-Sensing Ion Channels (ASICs), an H+-gated subgroup of epithelial sodium channel/ degenerin (ENaC/DEG) family, are almost ubiquitous in the mammalian nervous systems and are activated in response to a drop in urrounding tissue pH. ASICs exist in the neural or non-neural tissues. They have also now emerged as key receptors for extracellular protons and represent their diverse roles in the pathophysiology of pain, ischemic heart, ischemic stroke, gastrointestinal and psychiatric diseases. Systemic acidosis on the skeleton has long been known in that low pH exerts a direct stimulatory effect on multinucleated bone-resorbing osteoclasts. ASIC1a, a subtype of ASICs, was reported as been essential for the extracellular acidification-induced increase in [Ca2+]i levels in osteoclasts and was involved in differentiation of osteoclasts. However, there is a paucity of studies about the relationship of osteblasts and ASICs. To elucidate the role of ASICs in osteoblast activity, the study will demonstrate the the expression of ASICs in osteoblasts, and changes of bone metabolic markers expressed by treatment with antagonists of ASICs.