title: CHI3L1 regulation of inflammation and the effects on osteogenesis in a Staphylococcus aureus-induced murine model of osteomyelitis.
abstract: Osteomyelitis is an inflammation of the bone and bone marrow that occurs as a consequence of infections mainly attributed to Staphylococcus aureus. In a previous study, we found that expression of the chitinase 3-like 1 (CHI3L1) gene affected mineralization of MC3T3-E1 cells infected with S. aureus and there was increased expression of CHI3L1 in the blood of osteomyelitis patients. In the present study, to further investigate the role of CHI3L1 in osteomyelitis, we developed an S. aureus-induced murine model of the disease. We found that the expression of CHI3L1 was significantly up-regulated in femurs of mice infected with S. aureus compared with mice inoculated with a PBS control. To investigate these results further, we performed a CHI3L1 knock-down by lentivirus-mediated RNA interference in mice. Micro-computed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover, and femurs of CHI3L1 short hairpin RNA (shRNA-CHI3L1)-injected mice infected with S. aureus have significantly less cortical bone destruction when compared with control mice infected with S. aureus. Inhibition of CHI3L1 also decreased inflammation by reducing levels of proinflammatory cytokines and promoted the process of osteogenesis. The Notch signaling pathway has been shown to play an important role in modulating the differentiation of osteoblasts and osteoclasts. Our study showed that Notch1, Jagged1 and Hes1 expression significantly decreased in mice infected with S. aureus compared with the control, and shRNA-CHI3L1 could increase their level in S. aureus-infected mice. This research indicates that inhibition of CHI3L1 can reduce the debilitating effects of S. aureus in a murine model of osteomyelitis.
authors.affiliation: Kunming Medical University, Yunnan Province, China.|School of Basic Medical Sciences, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China.
authors.forename: XueQiu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Outpatient Department, The 2nd Affiliated Hospital of Kunming Medical University, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Orthopaedics, Kunming General Hospital of PLA, China.
authors.forename: XiaoQing
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Orthopaedics, Kunming General Hospital of PLA, China.
authors.forename: JianPing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Kunming General Hospital of PLA, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Kunming Medical University, Yunnan Province, China.|Department of Orthopaedics, Kunming General Hospital of PLA, China.
authors.forename: YongQing
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, Kunming General Hospital of PLA, China.|College of Life Science and Technology, Kunming University of Science and Technology, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001862:Bone Resorption; D000071451:Chitinase-3-Like Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005269:Femur / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D007249:Inflammation / Q000503:physiopathology; D000072100:Jagged-1 Protein / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000378:metabolism; D010019:Osteomyelitis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D016207:Cytokines; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C497762:Notch1 protein, mouse; D034741:RNA, Small Interfering; D051881:Receptor, Notch1
keywords: CHI3L1; Notch signaling; osteogenesis; osteomyelitis