title: Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.
abstract: It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation.
authors.affiliation: a Department of Orthopaedics , The Second Affiliated Hospital of Soochow University , Suzhou , Jiangsu Province , China.|b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Peng
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Kang
authors.initials: K
authors.lastname: Hui
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hao
authors.affiliation: c Intensive Care Unit , The Second Affiliated Hospital of Soochow University , Suzhou , Jiangsu Province , China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Peng
authors.affiliation: d Department of Rehabilitation, 359th Hospital of Chinese People's Liberation Army , Zhen Jiang , Jiangsu Province , China.
authors.forename: Qian Xing
authors.initials: QX
authors.lastname: Gao
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Guo
authors.initials: G
authors.lastname: Lei
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Min
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Qi
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Chen
authors.initials: C
authors.lastname: Bo
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Qian Nian
authors.initials: QN
authors.lastname: Dong
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Zhou Han
authors.initials: ZH
authors.lastname: Bing
authors.affiliation: a Department of Orthopaedics , The Second Affiliated Hospital of Soochow University , Suzhou , Jiangsu Province , China.
authors.forename: Xu You
authors.initials: XY
authors.lastname: Jia
authors.affiliation: b Shanghai Institute of Traumatology and Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Ruijin Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Deng Lian
authors.initials: DL
authors.lastname: Fu
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology; D015519:Bone Density; D016723:Bone Remodeling; D001862:Bone Resorption / Q000150:complications / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005269:Femur / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D010024:Osteoporosis / Q000139:chemically induced* / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013311:Streptozocin
chemical_list: D043925:Angiogenesis Inducing Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; D013311:Streptozocin
keywords: Angiogenesis; HIF-1α; bone formation; bone resorption; osteoporosis; type 1 diabetes