L-serine regulation of RANK signaling machinery and its role in bone metabolism

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Osteoclasts play central roles in the development and remodeling of bone. In addition to the stimulation by RANKL, serine in the culture medium is necessary for the in vitro differentiation of osteoclasts from their precursors. We conducted a series of experiments to understand the regulatory mechanism of osteoclast differentiation by serine as well as its physiological significance, and found the association between serine transport and cellular uptake of other amino acids and serine deprivation suppresses the differentiation through the reduction of other several intracellular amino acids and the downregulation of RANKL receptor, RANK.