{"doi":"10.1091/mbc.e02-06-0354","title":"Osteopontin Deficiency Produces Osteoclast Dysfunction Due to Reduced CD44 Surface Expression","abstract":"<jats:p>Osteopontin (OPN) was expressed in murine wild-type osteoclasts, localized to the basolateral, clear zone, and ruffled border membranes, and deposited in the resorption pits during bone resorption. The lack of OPN secretion into the resorption bay of avian osteoclasts may be a component of their functional resorption deficiency in vitro. Osteoclasts deficient in OPN were hypomotile and exhibited decreased capacity for bone resorption in vitro. OPN stimulated CD44 expression on the osteoclast surface, and CD44 was shown to be required for osteoclast motility and bone resorption. Exogenous addition of OPN to OPN−/− osteoclasts increased the surface expression of CD44, and it rescued osteoclast motility due to activation of the α<jats:sub>v</jats:sub>β<jats:sub>3</jats:sub>integrin. Exogenous OPN only partially restored bone resorption because addition of OPN failed to produce OPN secretion into resorption bays as seen in wild-type osteoclasts. As expected with these in vitro findings of osteoclast dysfunction, a bone phenotype, heretofore unappreciated, was characterized in OPN-deficient mice. Delayed bone resorption in metaphyseal trabeculae and diminished eroded perimeters despite an increase in osteoclast number were observed in histomorphometric measurements of tibiae isolated from OPN-deficient mice. The histomorphometric findings correlated with an increase in bone rigidity and moment of inertia revealed by load-to-failure testing of femurs. These findings demonstrate the role of OPN in osteoclast function and the requirement for OPN as an osteoclast autocrine factor during bone remodeling.</jats:p>","journal":"Molecular Biology of the Cell","year":2003,"id":629060,"datarank":0.8282191376793371,"base_score":5.521460917862246,"endowment":5.521460917862246,"self_citation_contribution":0.8282191376793371,"citation_network_contribution":0.0,"self_endowment_contribution":0.8282191376793371,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":249,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":14,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1629012,"name":"N. Kizer","orcid":null,"position":1,"is_corresponding":false},{"id":1629013,"name":"R. Biswas","orcid":null,"position":2,"is_corresponding":false},{"id":1629014,"name":"U. Alvarez","orcid":null,"position":3,"is_corresponding":false},{"id":1629015,"name":"J. Strauss-Schoenberger","orcid":null,"position":4,"is_corresponding":false},{"id":1629016,"name":"L. Rifas","orcid":null,"position":5,"is_corresponding":false},{"id":1629017,"name":"S. R. Rittling","orcid":null,"position":6,"is_corresponding":false},{"id":1629018,"name":"D. T. Denhardt","orcid":null,"position":7,"is_corresponding":false},{"id":1629019,"name":"K. A. Hruska","orcid":null,"position":8,"is_corresponding":false},{"id":1629011,"name":"M. A. Chellaiah","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Osteopontin Deficiency Produces Osteoclast Dysfunction Due to Reduced CD44 Surface Expression","abstract":"<jats:p>Osteopontin (OPN) was expressed in murine wild-type osteoclasts, localized to the basolateral, clear zone, and ruffled border membranes, and deposited in the resorption pits during bone resorption. The lack of OPN secretion into the resorption bay of avian osteoclasts may be a component of their functional resorption deficiency in vitro. Osteoclasts deficient in OPN were hypomotile and exhibited decreased capacity for bone resorption in vitro. OPN stimulated CD44 expression on the osteoclast surface, and CD44 was shown to be required for osteoclast motility and bone resorption. Exogenous addition of OPN to OPN−/− osteoclasts increased the surface expression of CD44, and it rescued osteoclast motility due to activation of the α<jats:sub>v</jats:sub>β<jats:sub>3</jats:sub>integrin. Exogenous OPN only partially restored bone resorption because addition of OPN failed to produce OPN secretion into resorption bays as seen in wild-type osteoclasts. As expected with these in vitro findings of osteoclast dysfunction, a bone phenotype, heretofore unappreciated, was characterized in OPN-deficient mice. Delayed bone resorption in metaphyseal trabeculae and diminished eroded perimeters despite an increase in osteoclast number were observed in histomorphometric measurements of tibiae isolated from OPN-deficient mice. The histomorphometric findings correlated with an increase in bone rigidity and moment of inertia revealed by load-to-failure testing of femurs. These findings demonstrate the role of OPN in osteoclast function and the requirement for OPN as an osteoclast autocrine factor during bone remodeling.</jats:p>","is_dataset_classified":null,"base_score":5.521460917862246,"endowment":5.521460917862246,"datacite_reuse_total":14,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12529435","pmcid":"PMC140236","openalex_id":"https://openalex.org/W2121793520","authors":[],"funders":[{"funder_name":"NIAMS NIH HHS","grant_id":"AR41677","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA72740","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"ES06897","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR046292","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R56 AR046292","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"AR44434","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK09976","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"AR39561","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR041677","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"AR46292","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P01 DK009976","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01AR044434-03","title":"OSTEOPONTIN SIGNALING--MECHANISM AND CONSEQUENCES"},{"funder_name":"National Institutes of Health","grant_id":"5P01DK009976-28","title":"PATHOPHYSIOLOGY OF RENAL DISEASE AND UREMIA"},{"funder_name":"National Institutes of Health","grant_id":"5R01AR046292-03","title":"GELSOLIN BASED SIGNALING IN OSTEOCLAST FUNCTION"},{"funder_name":"National Institutes of Health","grant_id":"5R01AR041677-02","title":"INTEGRIN, AVB3, IN OSTEOCLAST PRECURSOR"},{"funder_name":"National Institutes of Health","grant_id":"2R01AR039561-05","title":"HORMONAL REGULATION OF BONE CELL FUNCTION"}],"total_grants":16,"fwci":9.7867,"citation_percentile":0.98887049,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":10},{"year":2014,"count":7},{"year":2015,"count":11},{"year":2016,"count":8},{"year":2017,"count":7},{"year":2018,"count":12},{"year":2019,"count":14},{"year":2020,"count":10},{"year":2021,"count":18},{"year":2022,"count":6},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":10},{"year":2026,"count":5}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=1467&context=open_access_pubs","host_type":"repository"},{"url":"https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=1467&context=open_access_pubs","host_type":"repository"},{"url":"https://digitalcommons.wustl.edu/open_access_pubs/468","host_type":"repository"},{"url":"https://doi.org/10.1091/mbc.e02-06-0354","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12529435","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/140236","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc140236?pdf=render","host_type":""},{"url":"https://dx.doi.org/10.1091/mbc.e02-06-0354","host_type":""},{"url":"https://doi.org/https://doi.org/10.1091/mbc.E02-06-0354","host_type":""}],"fields_of_study":["Bone and Dental Protein Studies","Bone Metabolism and Diseases","Bone health and treatments","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Antibodies","Bone and Bones","Cell Line","Cell Movement","Hyaluronan Receptors","Integrin alphaVbeta3","Mice","Osteoclasts","Osteopontin","Sialoglycoproteins","rhoA GTP-Binding Protein"],"mesh_terms":["Animals","Antibodies","Bone and Bones","Cell Line","Cell Movement","Osteoclasts","Sialoglycoproteins","Hyaluronan Receptors","rhoA GTP-Binding Protein","Integrin alphaVbeta3","Mice","Osteopontin"],"keywords":["Osteoclast","Bone resorption","Osteopontin","Resorption","Endocrinology","Internal medicine","Biology","Bone remodeling","Cell biology","In vitro","Medicine","Biochemistry","Sialoglycoproteins","Osteoclasts","Integrin alphaVbeta3","Antibodies","Bone and Bones","Cell Line","Mice","Hyaluronan Receptors","Cell Movement","Medicine and Health Sciences","Animals","rhoA GTP-Binding Protein"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.14313755.v1","title":"Additional file 1 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313755","title":"Additional file 1 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313758.v1","title":"Additional file 2 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313758","title":"Additional file 2 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313761.v1","title":"Additional file 3 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313761","title":"Additional file 3 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313764.v1","title":"Additional file 4 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313764","title":"Additional file 4 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313767.v1","title":"Additional file 5 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313767","title":"Additional file 5 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313770.v1","title":"Additional file 6 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313770","title":"Additional file 6 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313773.v1","title":"Additional file 7 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14313773","title":"Additional file 7 of Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T16:20:08.282100Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}