title: IL-6 Contributes to the Defective Osteogenesis of Bone Marrow Stromal Cells from the Vertebral Body of the Glucocorticoid-Induced Osteoporotic Mouse.
abstract: Osteoporosis is one of the most prevalent skeletal system diseases. It is characterized by a decrease in bone mass and microarchitectural changes in bone tissue that lead to an attenuation of bone resistance and susceptibility to fracture. Vertebral fracture is by far the most prevalent osteoporotic fracture. In the musculoskeletal system, osteoblasts, originated from bone marrow stromal cells (BMSC), are responsible for osteoid synthesis and mineralization. In osteoporosis, BMSC osteogenic differentiation is defective. However, to date, what leads to the defective BMSC osteogenesis in osteoporosis remains an open question. In the current study, we made attempts to answer this question. A mouse model of glucocorticoid-induced osteoporosis (GIO) was established and BMSC were isolated from vertebral body. The impairment of osteogenesis was observed in BMSC of osteoporotic vertebral body. The expression profiles of thirty-six factors, which play important roles in bone metabolisms, were compared through antibody array between normal and osteoporotic BMSC. Significantly higher secretion level of IL-6 was observed in osteoporotic BMSCs compared with normal control. We provided evidences that IL-6 over-secretion impaired osteogenesis of osteoporotic BMSC. Further, it was observed that β-catenin activity was inhibited in response to IL-6 over-secretion. More importantly, in vivo administration of IL-6 neutralizing antibody was found to be helpful to rescue the osteoporotic phenotype of mouse vertebral body. Our study provides a deeper insight into the pathophysiology of osteoporosis and identifies IL-6 as a promising target for osteoporosis therapy.
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.|Department of Orthopedics, Huai'an First People's Hospital, Huai'an, 223300, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Huaiyin hospital of Huai'an city, Huai'an, 223300, People's Republic of China.
authors.forename: Zong-Yu
authors.initials: ZY
authors.lastname: Zhou
authors.affiliation: Department of pediatrics, Huai'an First People's Hospital, Huai'an, 223300, People's Republic of China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Yang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000008:administration & dosage; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011239:Prednisolone / Q000008:administration & dosage; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013131:Spine / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051176:beta Catenin / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D057134:Antibodies, Neutralizing; D005938:Glucocorticoids; D015850:Interleukin-6; D011239:Prednisolone; D050796:STAT3 Transcription Factor; D051176:beta Catenin; D000093242:Interleukin-6 Inhibitors; C495267:CTNNB1 protein, mouse; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse