title: Bone marrow transplantation improves autoinflammation and inflammatory bone loss in SH3BP2 knock-in cherubism mice.
abstract: Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2(KI/KI)) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2(KI/KI) mice. Bone marrow (BM) cells from wild-type (Sh3bp2(+/+)) mice were transplanted to 6-week-old Sh3bp2(KI/KI) mice with developing inflammation and to 10-week-old Sh3bp2(KI/KI) mice with established inflammation. Six-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10weeks after BMT compared to Sh3bp2(KI/KI) mice transplanted with Sh3bp2(KI/KI) BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20weeks in 6-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2(KI/KI) mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients.
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, MO 64108, USA. Electronic address: yoshitakat@umkc.edu.
authors.forename: Teruhito
authors.initials: T
authors.lastname: Yoshitaka
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, MO 64108, USA. Electronic address: kittakam@umkc.edu.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kittaka
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, MO 64108, USA; Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734, Japan; Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734, Japan. Electronic address: shu1222@hotmail.co.jp.
authors.forename: Shu
authors.initials: S
authors.lastname: Ishida
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, MO 64108, USA; Department of Periodontal Medicine, Division of Applied Life Science, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734, Japan; Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734, Japan. Electronic address: mizuno@hiroshima-u.ac.jp.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, MO 64108, USA. Electronic address: mukai09@gmail.com.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mukai
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, MO 64108, USA. Electronic address: uekiy@umkc.edu.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ueki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D001862:Bone Resorption / Q000473:pathology*; D002636:Cherubism / Q000473:pathology*; D005260:Female; D055879:Gene Knock-In Techniques; D007249:Inflammation / Q000097:blood / Q000473:pathology* / Q000628:therapy*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C484644:Sh3bp2 protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: Autoinflammation; Bone loss; Bone marrow transplantation; Cherubism; SH3BP2