title: Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts.
abstract: CD68 is a member of the lysosome associated membrane protein (LAMP) family that is restricted in its expression to cells of the monocyte/macrophage lineage. This lineage restriction includes osteoclasts, and, while previous studies of CD68 in macrophages and dendritic cells have proposed roles in lipid metabolism, phagocytosis, and antigen presentation, the expression and function of CD68 in osteoclasts have not been explored. In this study, we investigated the expression and localization of CD68 in macrophages and osteoclasts in response to the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL). We found that M-CSF stimulates CD68 expression and RANKL alters the apparent molecular weight of CD68 as measured by Western immunoblotting. In addition, we explored the significance of CD68 expression in osteoclasts by generating mice that lack expression of CD68. These mice have increased trabecular bone, and in vitro assessment of CD68(-/-) osteoclasts revealed that, in the absence of CD68, osteoclasts demonstrate an accumulation of intracellular vesicle-like structures, and do not efficiently resorb bone. These findings demonstrate a role for CD68 in the function of osteoclasts, and future studies will determine the mechanistic nature of the defects seen in CD68(-/-) osteoclasts.
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors: Jason W
authors: JW
authors: Ashley
authors: Zhenqi
authors: Z
authors: Shi
authors: Haibo
authors: H
authors: Zhao
authors: Xingsheng
authors: X
authors: Li
authors: Robert A
authors: RA
authors: Kesterson
authors: Xu
authors: X
authors: Feng
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics* / Q000378:metabolism; D015519:Bone Density; D001854:Bone Marrow Cells / Q000473:pathology; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology*; D002417:Cattle; D002478:Cells, Cultured; D017353:Gene Deletion; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology*; D010012:Osteogenesis; D010641:Phenotype; D021381:Protein Transport; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C081026:CD68 protein, mouse; D000097382:CD68 Molecule