title: Deubiquitinase MYSM1 Is Essential for Normal Bone Formation and Mesenchymal Stem Cell Differentiation.
abstract: Deubiquitinase MYSM1 has been shown to play a critical role in hematopoietic cell differentiation and hematopoietic stem cell (HSC) maintenance. Mesenchymal stem cells (MSCs) are multipotent stromal cells within the bone marrow. MSCs are progenitors to osteoblasts, chondrocytes, adipocytes, and myocytes. Although, MSCs have been extensively studied, the roles of MYSM1 in these cells remain unclear. Here we describe the function of MYSM1 on MSC maintenance and differentiation. In this report, we found that Mysm1-/- mice had a lower bone mass both in long bone and calvaria compared with their control counterpart. Preosteoblasts from Mysm1-/- mice did not show changes in proliferation or osteogenesis when compared to WT mice. Conversely, Mysm1-/- MSCs showed enhanced autonomous differentiation and accelerated adipogenesis. Our results demonstrate that MYSM1 plays a critical role in MSC maintenance and differentiation. This study also underscores the biological significance of deubiquitinase activity in MSC function. Mysm1 may represent a potential therapeutic target for controlling MSC lineage differentiation, and possibly for the treatment of metabolic bone diseases such as osteoporosis.
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, 28Fuxing Road, HaidianDistrict, Beijing 100850, P.R. China.|Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.|Department of Stomatology, The 309th Hospital of Chinese People's Liberation Army, Beijing, 100091, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, 28Fuxing Road, HaidianDistrict, Beijing 100850, P.R. China.|Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Cardiovax LLC, 10100 Santa Monica Blvd, Los Angeles, California, 90067, USA.
authors.forename: Suzi
authors.initials: S
authors.lastname: Sanchez
authors.affiliation: Department of Anesthesiology, Beijing Aiyuhua Hospital for Children and Women, 2 South Street, Beijing economic and Technological Development Zone, Beijing 100176, P.R. China.
authors.forename: Dian-Chao
authors.initials: DC
authors.lastname: Cui
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, 28Fuxing Road, HaidianDistrict, Beijing 100850, P.R. China.|Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Rui-Jie
authors.initials: RJ
authors.lastname: Dang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Lin
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Beijing Research Institutes of Traumatology and Orthopaedics, Beijing, 100035 P.R. China.
authors.forename: Da-Fu
authors.initials: DF
authors.lastname: Chen
authors.affiliation: Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033, USA.
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Jiang
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, 28Fuxing Road, HaidianDistrict, Beijing 100850, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wen
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D015519:Bone Density / Q000235:genetics; D001842:Bone and Bones / Q000002:abnormalities; D019070:Cell Lineage / Q000235:genetics; D010450:Endopeptidases / Q000172:deficiency / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics; D015534:Trans-Activators; D064570:Ubiquitin-Specific Proteases
chemical_list: D015534:Trans-Activators; D010450:Endopeptidases; C570173:MYSM1 protein, mouse; D064570:Ubiquitin-Specific Proteases