title: Mesenchymal progenitors in osteopenias of diverse pathologies: differential characteristics in the common shift from osteoblastogenesis to adipogenesis.
abstract: Osteoporosis is caused by pathologic factors such as aging, hormone deficiency or excess, inflammation, and systemic diseases like diabetes. Bone marrow stromal cells (BMSCs), the mesenchymal progenitors for both osteoblasts and adipocytes, are modulated by niche signals. In differential pathologic states, the pathological characteristics of BMSCs to osteoporoses and functional differences are unknown. Here, we detected that trabecular bone loss co-existed with increased marrow adiposity in 6 osteoporotic models, respectively induced by natural aging, accelerated senescence (SAMP6), ovariectomy (OVX), type 1 diabetes (T1D), excessive glucocorticoids (GIOP) and orchidectomy (ORX). Of the ex vivo characteristics of BMSCs, the colony-forming efficiency and the proliferation rate in aging, SAMP6, OVX, GIOP and ORX models decreased. The apoptosis and cellular senescence increased except in T1D, with up-regulation of p53 and p16 expression. The osteogenesis declined except in GIOP, with corresponding down-regulation of Runt-related transcription factor 2 (RUNX2) expression. The adipogenesis increased in 6 osteoporotic models, with corresponding up-regulation of Peroxisome proliferator activated receptor gamma (PPARγ) expression. These findings revealed differential characteristics of BMSCs in a common shift from osteoblastogenesis to adipogenesis among different osteoporoses and between sexes, and provide theoretical basis for the functional modulation of resident BMSCs in the regenerative therapy for osteoporosis.
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Sui
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Chenghu
authors.initials: C
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Dental Materials, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|State Key Laboratory of Military Stomatology, Department of Dental Materials, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.|Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an 710032, Shaanxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D017667:Adipocytes / Q000473:pathology; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000473:pathology*; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology