title: The interaction of MMP-2/B7-H3 in human osteoporosis.
abstract: The immune costimulatory molecule B7-H3 has been shown to be involved in the regulation of murine bone formation. However, the role of B7-H3 in bone metabolic diseases remains unknown. In our study, matrix metalloproteinase 2 (MMP-2) and soluble B7-H3 (sB7-H3) were found to be correlatively up-regulated in the sera of osteoporosis patients. Furthermore, our results showed that MG63 cells treated with MMP-2 inhibitors produced lower amounts of sB7-H3 while cells with recombinant MMP-2 had an increased membrane B7-H3 (mB7-H3) shedding. Therefore, elevated MMP-2 levels resulted in an elevation of serum sB7-H3 and reduction of osteoblastic mB7-H3. B7-H3 knockdown in MG63 cells significantly decreased osteoblastic markers and substantially decreased the number of mineralized nodules after 21days. Thus, B7-H3-deficient MG63 cells exhibited impaired bone formation. These results suggest that mB7-H3 is required for the later phases of osteoblast differentiation and that MMP-2/B7-H3 plays a negative regulatory role in osteoporosis.
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Feng
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Zhuqiu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Mao
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China.
authors.forename: Peijuan
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China. Electronic address: yrhzl@hotmail.com.
authors.forename: Yae
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu Province, China. Electronic address: anne_yrh@sohu.com.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Yan
mesh_terms: D060887:B7 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis / Q000201:enzymology / Q000503:physiopathology*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Bone; Matrix metalloproteinases; Osteoporosis; Soluble B7-H3