title: Syntaxin 4a Regulates Matrix Vesicle-Mediated Bone Matrix Production by Osteoblasts.
abstract: Osteoblasts secrete matrix vesicles and proteins to bone surfaces, but the molecular mechanisms of this secretion system remain unclear. The present findings reveal the roles of important genes in osteoblasts involved in regulation of extracellular matrix secretion. We especially focused on "soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor" (SNARE) genes and identified notable Syntaxin 4a (Stx4a) expression on the basolateral side of the plasma membrane of osteoblasts. Furthermore, Stx4a overexpression was found to increase mineralization by osteoblastic cells, whereas Stx4a knockdown reduced levels of mineralization. Also, BMP-4 and IGF-1 induced the localization of Stx4a to the basolateral side of the cells. To examine the function of Stx4a in osteoblasts, we generated osteoblast-specific Stx4a conditional knockout mice, which demonstrated an osteopenic phenotype due to reduced matrix secretion. Bone mineral density, shown by peripheral quantitative computed tomography (pQCT), was reduced in the femur metaphyseal and diaphyseal regions of Stx4a osteoblast-specific deficient mice, whereas bone parameters, shown by micro-computed tomography (μCT) and bone histomorphometric analysis, were also decreased in trabecular bone. In addition, primary calvarial cells from those mice showed decreased mineralization and lower secretion of matrix vesicles. Our findings indicate that Stx4a plays a critical role in bone matrix production by osteoblasts. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Challenge to Intractable Oral Diseases, Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Challenge to Intractable Oral Diseases, Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Michikami
authors.affiliation: Challenge to Intractable Oral Diseases, Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Jirouta
authors.initials: J
authors.lastname: Kitagaki
authors.affiliation: Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hata
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Hyogo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Hyogo, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Preventive Dentistry, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Amano
authors.affiliation: Challenge to Intractable Oral Diseases, Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Osaka, Japan.|Department of Oral Anatomy and Developmental Biology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakisaka
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density; D001857:Bone Matrix / Q000378:metabolism*; D002113:Calcification, Physiologic; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D012886:Skull / Q000166:cytology; D013977:Tibia / Q000000981:diagnostic imaging; D055114:X-Ray Microtomography
chemical_list: D050765:Qa-SNARE Proteins
keywords: BONE MATRIX PRODUCTION; BONE MINERALIZATION; EXOCYTOSIS; MEMBRANE TRAFFICKING; SNARE; SYNTAXIN