Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice

Wadhwa, Sunil; Bi, Yanming; Ortiz, Ana T; Embree, Mildred C.; Kilts, Tina M.; Iozzo, Renato V.; Opperman, Lynne A.; Young, Marian F.

doi:10.1016/j.bone.2006.11.003

Cited by 24 publications

(35 citation statements)

References 39 publications

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“…Decorin and biglycan are considered to regulate calvarial bone formation in developmental processes by interacting with BMPs from the study of knockout mice (Wadhwa et al, 2007). The present study showed that the differentiation of MC3T3-E1 cells, established from murine calvaria, is controlled by CS or DS chains of PGs in vitro, supporting the in vivo phenotype alteration.…”

Section: Journal Of Cellular Physiology C H O N D R O I T I N S U L Fmentioning

confidence: 50%

Oversulfated chondroitin sulfate‐E binds to BMP‐4 and enhances osteoblast differentiation

Miyazaki

Miyauchi²,

Tawada³

et al. 2008

Journal Cellular Physiology

109

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Small leucine-rich proteoglycans, such as biglycan, and their side chain sulfated glycosaminoglycans (GAGs), have been suggested to be involved in bone formation and mineralization processes. The present study was designed to investigate whether chondroitin sulfate (CS), one of the GAG, and its oversulfated structures coupled with bone morphogenetic protein-4 (BMP-4) alter the differentiation and subsequent mineralization of MC3T3-E1 osteoblastic cells. CS-E, one of the oversulfated CS structure, enhanced cell growth, alkaline phosphatase (ALP) activity, collagen deposition, and mineralization whereas heparin enhanced only ALP activity and mineralization. As well as CS-E, CS-H, and CPS also enhanced the mineralization of the cells. CS-E enhanced the mineralization of the cells by interacting with protein in the conditioned medium. CS-E induced mineralization was significantly inhibited by an antibody against BMP-4. The addition of exogenous BMP-4 further increased the capacity of CS-E to enhance mineralization. Fluorescence correlation spectroscopy method using fluoresceinamine-labeled GAG revealed that the oversulfated GAGs have a high affinity for BMP-4. The disaccharide analysis of the cells indicated that MC3T3-E1 cells are capable of producing oversulfated structures of CS by themselves. The lack of CS from the cells after chondroitinase treatment resulted in the inhibition of mineralization. These results in the present study indicate that oversulfated CS, which possesses 4,6-disulfates in N-acetyl-galactosamine, binds to BMP-4 and promotes osteoblast differentiation and subsequent mineralization.

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Section: Journal Of Cellular Physiology C H O N D R O I T I N S U L Fmentioning

confidence: 50%

Oversulfated chondroitin sulfate‐E binds to BMP‐4 and enhances osteoblast differentiation

Miyazaki

Miyauchi²,

Tawada³

et al. 2008

Journal Cellular Physiology

109

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“…In addition to the tendon, several studies suggest functional compensation for decorin by biglycan in single null models. For example, the posterior frontal suture of the developing calvaria fuses normally in the absence of either decorin or biglycan, but fails to fuse in mice null for both SLRPs [25]. Mice that lack both decorin and biglycan exhibit a collagen fibril morphology that is significantly more abnormal than either single deficiency, which supports the hypothesis that they have overlapping functions that permit functional compensation in single null mice [8, 23].…”

Section: Introductionmentioning

confidence: 85%

Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons

et al. 2017

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The small leucine-rich proteoglycans (SLRPs), decorin and biglycan, are key regulators of collagen fibril and matrix assembly. The goal of this work was to elucidate the roles of decorin and biglycan in tendon homeostasis. Our central hypothesis is that decorin and biglycan expression in the mature tendon would be critical for the maintenance of the structural and mechanical properties of healthy tendons. Defining the function(s) of these SLRPs in tendon homeostasis requires that effects in the mature tendon be isolated from their influence on development. Thus, we generated an inducible knockout mouse model that permits genetic ablation of decorin and biglycan expression in the mature tendon, while maintaining normal expression during development. Decorin and biglycan expression were knocked out in the mature patellar tendon with the subsequent turnover of endogenous SLRPs deposited prior to induction. The acute absence of SLRP expression was associated with changes in fibril structure with a general shift to larger diameter fibrils in the compound knockout tendons, together with fibril diameter heterogeneity. In addition, tendon mechanical properties were altered. Compared to wild-type controls, acute ablation of both genes resulted in failure of the tendon at lower loads, decreased stiffness, a trend toward decreased dynamic modulus, as well as a significant increase in percent relaxation and tissue viscosity. Collagen fiber realignment was also increased with a delayed and slower in response to load in the absence of expression. These structural and functional changes in response to an acute loss of decorin and biglycan expression in the mature tendon demonstrate a significant role for these SLRPs in adult tendon homeostasis.

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“…Decorin is thought to regulate Transforming growth factor beta (TGFB) bioavailability and mutations in this gene have been linked to Marfan syndrome [37], [38]. Decorin has also been identified at the cranial suture with importance for suture formation and growth linked to its expression [39]. In addition, a study investigating the effects of FGF2 administration to Crouzon Syndrome (FGFr Autosomal Dominant Craniosynostosis Syndrome) patient derived parietal bone osteoblasts suggested an inverse relationship between FGF2 and DCN [40].…”

Section: Discussionmentioning

confidence: 99%

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

et al. 2013

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The incidence of craniosynostosis is one in every 1,800–2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis.

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Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice

Cited by 24 publications

References 39 publications

Oversulfated chondroitin sulfate‐E binds to BMP‐4 and enhances osteoblast differentiation

Oversulfated chondroitin sulfate‐E binds to BMP‐4 and enhances osteoblast differentiation

Decorin and biglycan are necessary for maintaining collagen fibril structure, fiber realignment, and mechanical properties of mature tendons

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

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