title: Staphylococcal protein A promotes osteoclastogenesis through MAPK signaling during bone infection.
abstract: Bone infection is a common and serious complication in the orthopedics field, which often leads to excessive bone destruction and non-union. Osteoclast is the only type of cells which have the function of bone resorption. Its over activation is closely related to excessive bone loss. Staphylococcus aureus (S. aureus) is a major pathogen causing bone infection, which can produce a large number of strong pathogenic substances staphylococcal protein A (SPA). However, few studies were reported about the effects of SPA on osteoclastogenesis. In our study, we observed that S. aureus activated osteoclasts and promoted bone loss in bone infection specimens. Then, we investigated the effects of SPA on RANKL-induced osteoclastogenesis in vitro, the results revealed that SPA promoted osteoclastic differentiation and fusion, and enhanced osteoclastic bone resorption. In addition, we also showed that SPA upregulated the expression of NFATc1 and c-FOS through the activation of MAPK signaling to promote osteoclastogenesis. Our findings might help us better understand the pathogenic role of S. aureus in bone infection and develop new therapeutic strategies for infectious bone diseases.
authors.affiliation: Center of Trauma of Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center of Trauma of Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China.
authors.forename: Ce
authors.initials: C
authors.lastname: Dou
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Dong
authors.affiliation: Center of Trauma of Daping Hospital, Third Military Medical University, Chongqing, China.|State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-6832-6371
authors.initials: J
authors.lastname: Fei
mesh_terms: D000818:Animals; D017209:Apoptosis; D016723:Bone Remodeling; D001862:Bone Resorption / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D001842:Bone and Bones / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D004789:Enzyme Activation; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D010019:Osteomyelitis / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D013205:Staphylococcal Protein A / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D013205:Staphylococcal Protein A; C505689:Tnfsf11 protein, mouse; D020928:Mitogen-Activated Protein Kinases
keywords: MAP Kinase; bone resorption; osteoclast; staphylococcal protein A