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Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts. However, the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood. Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion. Single cell RNA sequencing-based analyses suggested that activation of parts of the apoptotic machinery accompanied the differentiation of osteoclast precursors into mature multinucleated osteoclasts. A subsequent characterization of osteoclast precursors confirmed that RANKL-mediated activation of caspase-8 promoted the non-apoptotic cleavage and activation of downstream effector caspases that translocated to the plasma membrane where they triggered activation of the phospholipid scramblase Xkr8. Xkr8-mediated exposure of phosphatidylserine, in turn, aided cellular fusion of osteoclast precursors and thereby allowed generation of functional multinucleated osteoclast syncytia and initiation of bone resorption. Pharmacological blockage or genetic deletion of caspase-8 accordingly interfered with fusion of osteoclasts and bone resorption resulting in increased bone mass in mice carrying a conditional deletion of caspase-8 in mononuclear osteoclast precursors. These data identify a novel pathway controlling osteoclast biology and bone turnover with the potential to serve as target for therapeutic intervention during diseases characterized by pathologic osteoclast-mediated bone loss. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis (1). Furthermore, PPARγ has been implicated as major catabolic regulator of bone mass in [...]

Among Weberians it is well known that Marianne Weber in her capacity as editor of the "Gesammelten Aufsätze zur Soziologie und Sozialpolitik," prepared the reprint of the two pieces titled "Die B&ouuml;rse," which Weber wrote in 1894 and 1896 for Friedrich Naumann's Göttinger Arbeiterbibliothek. Previously unknown was that already in Weber's lifetime two excerpts from these booklets were published in a reader especially addressed to businessmen. Of course, this discovery is of little importance for our knowledge of the life and work of Max Weber, but it is not entirely uninteresting. Those interested in studying this discovery in more detail, especially in obtaining the list of changes in Weber's text, the relevant excerpts from Mollat's reader, the correspondence and other documents should write to Arbeitsstelle der Max Weber Gesamtausgabe at Germany.