Characterization of the Microtubule Organizing Centres in Osteoclasts

Osteoclasts are highly specialized, multinucleated cells responsible for the selective resorption of bone matrix during bone remodeling and the pathological bone destruction found in osteoporosis. Our study investigated the origin of microtubules during osteoclast differentiation and bone resorption. Microtubule nucleation is generally restricted to specific subcellular sites called microtubule organizing centres (MTOCs) and is primarily fulfilled by the centrosome in metazoan cells. While mononuclear osteoclast precursor cells contain centrosomal MTOCs, previous research has suggested that functional centrosomal MTOCs do not exist in multinucleated osteoclasts. Through live-cell imaging, immunofluorescence, and ultrastructural analyses, we observed that most, if not all centrosomes donated from precursor cells remained individually functional and clustered early during osteoclastogenesis. Furthermore, by visualizing Golgi reorganization and Golgi-derived microtubules, we identified the Golgi as a possible non-centrosomal MTOC that potentially facilitates polarized microtubule arrays in osteoclasts. Together these findings show that multinucleated osteoclasts employ unique centrosomal and non-centrosomal MTOCs to organize microtubules.M.Sc.2020-11-26 00:00:0