Genetic Ablation of CD68 Results in Mice with Increased Bone and Dysfunctional Osteoclasts

Hdl Handle:
http://hdl.handle.net/10675.2/679
Title:
Genetic Ablation of CD68 Results in Mice with Increased Bone and Dysfunctional Osteoclasts
Authors:
Ashley, Jason W. ( 0000-0003-1064-542X ) ; Shi, Zhenqi; Zhao, Haibo; Li, Xingsheng; Kesterson, Robert A.; Feng, Xu
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 CD68â /â 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 CD68â /â osteoclasts.
Editors:
McNeil, Paul L.
Citation:
PLoS One. 2011 Oct 3; 6(10):e25838
Issue Date:
3-Oct-2011
URI:
http://hdl.handle.net/10675.2/679
DOI:
10.1371/journal.pone.0025838
PubMed ID:
21991369
PubMed Central ID:
PMC3185056
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Cellular Biology and Anatomy Faculty Papers

Full metadata record

DC FieldValue Language
dc.contributor.authorAshley, Jason W.en_US
dc.contributor.authorShi, Zhenqien_US
dc.contributor.authorZhao, Haiboen_US
dc.contributor.authorLi, Xingshengen_US
dc.contributor.authorKesterson, Robert A.en_US
dc.contributor.authorFeng, Xuen_US
dc.contributor.editorMcNeil, Paul L.-
dc.date.accessioned2012-10-26T16:29:31Z-
dc.date.available2012-10-26T16:29:31Z-
dc.date.issued2011-10-3en_US
dc.identifier.citationPLoS One. 2011 Oct 3; 6(10):e25838en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21991369en_US
dc.identifier.doi10.1371/journal.pone.0025838en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/679-
dc.description.abstractCD68 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 CD68â /â 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 CD68â /â osteoclasts.en_US
dc.rightsAshley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectBoneen_US
dc.subjectBiochemistryen_US
dc.subjectCytochemistryen_US
dc.subjectCell Membraneen_US
dc.subjectMembrane Proteinsen_US
dc.subjectProteinsen_US
dc.subjectIntracellular Receptorsen_US
dc.subjectComputational Biologyen_US
dc.subjectMolecular Geneticsen_US
dc.subjectGene Regulationen_US
dc.subjectGene Expressionen_US
dc.subjectGeneticsen_US
dc.subjectMolecular Geneticsen_US
dc.subjectGene Identification and Analysisen_US
dc.subjectGene Regulationen_US
dc.subjectGene Expressionen_US
dc.subjectGene Functionen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectGene Expressionen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectBoneen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, CDen_US
dc.subject.meshAntigens, Differentiation, Myelomonocyticen_US
dc.subject.meshBone Densityen_US
dc.subject.meshBone Marrow Cellsen_US
dc.subject.meshBone Resorptionen_US
dc.subject.meshBone and Bonesen_US
dc.subject.meshCattleen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshGene Deletionen_US
dc.subject.meshMacrophagesen_US
dc.subject.meshMiceen_US
dc.subject.meshOsteoblastsen_US
dc.subject.meshOsteoclastsen_US
dc.subject.meshOsteogenesisen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshProtein Transporten_US
dc.titleGenetic Ablation of CD68 Results in Mice with Increased Bone and Dysfunctional Osteoclastsen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3185056en_US
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomy-
dc.contributor.corporatenameCollege of Graduate Studies-

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