L-serine starvation response in osteoclast precursors and its physiological significance in the bone marrow microenvironment

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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 activation of amino acid starvation response in the precursors by serine deprivation alone, low expression of serine biosynthetic enzymes, and importance of serine supplied by osteoblasts to osteoclasts in the bone marrow microenvironment.