title: Biglycan mediates suture expansion osteogenesis via potentiation of Wnt/β-catenin signaling.
abstract: Mechanical force across sutures is known to modulate suture osteogenesis. However, the underlying mechanisms still remain poorly understood. Biglycan is a component of extracellular matrix (ECM) that is postulated to release from ECM and function as a signaling molecule. Biglycan stimulates the bone formation through Wnt/β-catenin signaling. To investigate the involvement of biglycan and Wnt/β-catenin signaling in suture expansion osteogenesis, we observed the expansion force-induced response in mouse midpalatal suture expansion model in vivo, and the mechanical strain-induced response of Wnt/β-catenin signaling in biglycan-deficient calvarial osteoblasts in vitro. Our data showed that expansion force significantly enhanced new bone formation at the edge of midpalatal sutures. Stronger biglycan positive staining was visible at the edge of expanding midpalatal sutures. The spatio-temporal expression of biglycan was highly consistent with ALP and COL-1, which also coincided with new bone formation throughout the midpalatal suture expansion process. Both protein and mRNA levels of biglycan, β-catenin, and osteogenic markers including Runx2, ALP and COL-1 were increased together. In addition, mechanical strain sufficiently induced upregulation of osteoblastic biglycan, which was paralleled with the strain-induced potentiation of Wnt/β-catenin signaling and Runx2 transcriptional activity. However, silencing osteoblastic biglycan resulted in an attenuated increase in the expression of nuclear active β-catenin and Runx2 in response to mechanical strain. Our data demonstrated that biglycan as a component of ECM mediates suture expansion osteogenesis through the activation of Wnt/β-catenin signaling.
authors.affiliation: Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
authors.forename: Yongchu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China. Electronic address: zhangweibing@njmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China. Electronic address: weibingzhang.njmu@gmail.com.
authors.forename: Wei-Bing
authors.initials: WB
authors.lastname: Zhang
mesh_terms: D000818:Animals; D058578:Biglycan / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D013537:Sutures; D060449:Wnt Signaling Pathway
chemical_list: D058578:Biglycan
keywords: Biglycan; Osteoblast; Osteogenesis; Suture expansion; Wnt/β-catenin