Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix

Abstract

The extracellular matrix protein Fibulin-1 (Fbln1) has been shown to be involved in numerous processes including cardiovascular and lung development. Here we have examined the role of Fbln1 in bone formation. Alizarin red staining of skulls from Fbln1 deficient mice showed reduced mineralization of both membranous and endochondral bones. Micro CT (μCT) analysis of the calvarial bones (i.e., frontal, parietal and interparietal bones collectively) indicated that bone volume in Fbln1 nulls at neonatal stage P0 were reduced by 22% (p = 0.015). Similarly, Fbln1 null frontal bones showed a 16% (p = 0.035) decrease in bone volume, with a reduction in the interfrontal bone, and a discontinuity in the leading edge of the frontal bone. To determine whether Fbln1 played a role in osteoblast differentiation during bone formation, qPCR was used to measure the effects of Fbln1 deficiency on the expression of Osterix (Osx), a transcription factor essential for osteoblast differentiation. This analysis demonstrated that Osx mRNA was significantly reduced in Fbln1-deficient calvarial bones at developmental stages E16.5 (p = 0.049) and E17.5 (p = 0.022). Furthermore, the ability of BMP-2 to induce Osx expression was significantly diminished in Fbln1-deficient mouse embryo fibroblasts. Together, these findings indicate that Fbln1 is a new positive modulator of the formation of membranous bone and endochondral bone in the skull, acting as a positive regulator of BMP signaling.

CRYAB promotes osteogenic differentiation of human bone marrow stem cells via stabilizing β‐catenin and promoting the Wnt signalling

“…As determined by qRT‐PCR analysis, the expression of these genes was consistent with the dataset (Figure B and C). Previous studies have reported several of the above‐mentioned genes (CIDEC, MAOA, SAA1, SVEP1, FBLN2, ADARB1, ZBTB16, ANGPT1, FBLN1, FZD4, OMD, ABI3BP, RGS4, CXCL8) are closely related to bone homeostasis and the process of osteogenic differentiation, and these studies further supported the reliability of the dataset. To identify the BMSCs osteogenic differentiation‐related genes, we chose 10 of the other upregulated genes, namely EFHD1, FKBP5, APOD, ACTC1, SORT1, COMP, CLEC3B, CRYAB, WASF3, LMOD1, and downregulated their expression by specific siRNA in BMSCs (Figure D‐M).…”

Sustained release of VH and rhBMP-2 from nanoporous magnesium–zinc–silicon xerogels for osteomyelitis treatment and bone repair

“…32 In this study, the VH or rhBMP-2 release profiles clearly indicated the sustained release of VH or rhBMP-2 from n-MZS, whereas MZS showed an initial burst release. The large amount of VH or rhBMP-2 could be loaded into n-MZS by a physical adsorption process, which could avoid initial burst release of VH or rhBMP-2.…”

Identification of new regulators of embryonic patterning and morphogenesis in Xenopus gastrulae by RNA sequencing

“…Two other fibulin family genes have been reported to regulate TGF-β family signaling. Fibulin-1 regulates BMP signaling through direct binding to BMP-2 (Cooley et al, 2014), whereas Fibulin-3 inhibits TGF-β 1 signaling by interacting with TpRI/ALK-5 to prevent formation of a functional ligand-receptor complex (Tian et al, 2015). Fibulin-4 mutations are associated with patients with aortic aneurysms, arterial tortuosity and stenosis.…”