Transcriptional Regulation of the Collagenase Gene by Basic Fibroblast Growth Factor in Osteoblastic MC3T3-E1 Cells

Hurley, Marja M.; Marcello, K.; Abreu, Christine; Brinckerhoff, Constance E.; Bowik, C.; Hibbs, Margaret S.

doi:10.1006/bbrc.1995.2292

Cited by 28 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 In this study, gene expression of HGF and MMP-1, which both have anti-fibrogenetic activity, was markedly upregulated by FGF-2 in HTS-derived and normal fibroblasts. Unlike MMP-1, upregulation of HGF mRNA expression at 6 or 24 h (Figure 4) are much lower compared to at 5 days (Figure 3), suggesting indirect effects of FGF-2 on 30,31 and fibroblasts. 32 It was also shown that upregulation of MMP-1 mRNA in osteoblasts is mediated by the MAPK pathway and completely abrogated by MAPK phosphatase (inactivates ERK ¼ JNK4p38 MAPK), 33 although the signaling mechanism in dermal fibroblasts remains to be elucidated.…”

Section: Discussionmentioning

confidence: 89%

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Eto

Suga

Aoi

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

Although hypertrophic scars (HTSs) and keloids are challenging problems, their pathogenesis is not well understood, making therapy difficult. We showed that matrix metalloproteinase (MMP)-1 expression was downregulated in HTS compared with normal skin from the same patients, whereas type 1 and 3 collagen and transforming growth factor-b (TGF-b) were upregulated. These differences, however, were not seen in cultured fibroblasts, suggesting the involvement of microenvironmental factors in the pathogenesis of HTS. Fibroblast growth factor-2 (FGF-2) highly upregulated the expression of MMP-1 and hepatocyte growth factor (HGF) in both HTS-derived and control fibroblasts; the upregulation was reversed by extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors. An animal study using human HTS tissue implanted into nude mice indicated that controlled-release FGF-2 resulted in significantly less weight and decreased hydroxyproline content in HTS. Degradation of collagen fibers in FGF-2-treated HTS was also confirmed histologically. Western blotting showed that FGF-2-treated HTS expressed significantly higher MMP-1 protein than control. Decreased MMP-1 expression may be an important transcriptional change in HTS, and its reversal as well as upregulation of HGF by FGF-2 could be a new therapeutic approach for HTS.

show abstract

Section: Discussionmentioning

confidence: 89%

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Eto

Suga

Aoi

et al. 2012

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…This conclusion is supported by the fact that the osteogenic actions of TGF-␤1 and FGF-2 are closely related because: 1) each cytokine directly enhances the expression of the other; 2) TGF-␤1 potentiates the mitogenic effects of FGF-2 on osteoblast-like cells; and 3) TGF-␤1 potentiates the expression of type I collagen, the major component of the bone extracellular matrix. 30,[37][38][39][40] Moreover, we have shown that increased expression of TGF-␤1, similar to FGF-2, is temporally and spatially related to programmed sutural fusion and patency. 12,27 It is interesting to note that Mehrara and colleagues 18 demonstrated increased type I collagen production by cells derived from PF-associated dural tissues as compared to cells derived from the dural tissues underlying a patent cranial suture.…”

Section: Discussionmentioning

confidence: 88%

In Vivo Modulation of FGF Biological Activity Alters Cranial Suture Fate

Greenwald

Mehrara

Spector

et al. 2001

The American Journal of Pathology

View full text Add to dashboard Cite

Gain-of-function mutations in fibroblast growth factor receptors have been identified in numerous syndromes associated with premature cranial suture fusion. Murine models in which the posterior frontal suture undergoes programmed fusion after birth while all other sutures remain patent provide an ideal model to study the biomolecular mechanisms that govern cranial suture fusion. Using adenoviral vectors and targeted in utero injections in rats, we demonstrate that physiological posterior frontal suture fusion is inhibited using a dominant-negative fibroblast growth factor receptor-1 construct, whereas the normally patent coronal suture fuses when infected with a construct that increases basic fibroblast growth factor biological activity. Our data may facilitate the development of novel, less invasive treatment options for children with craniosynostosis. Gain-of-function mutations in the fibroblast growth factor receptors (FGF-Rs) have been identified in many syndromes that have craniosynostosis as their defining characteristic including Apert, Pfeiffer, and Crouzon syndromes. These syndromes are all characterized by craniosynostosis (ie, premature fusion of one or more cranial sutures) and varying degrees of extracranial skeletal abnormalities. 1 In vitro studies of these mutated FGF-Rs have identified at least two biomolecular mechanisms that mediate excess signaling by these receptors: 1) formation of receptor dimers in the absence of receptor ligand [ie, basic fibroblast growth factor (FGF), FGF-2] resulting in ligand-independent intracellular signaling; and 2) increased affinity of mutated receptors for ligand. 2-6 Increased FGF-biological activity is thought to lead to the premature fusion of cranial sutures and the dysmorphic craniofacial phenotype associated with these syndromes. To date, however, direct evidence supporting this hypothesis has been lacking.To understand the events that lead to premature cranial suture fusion, numerous investigators have relied on animal models of cranial suture fusion. Murine suture development, in which the posterior frontal (PF) suture undergoes programmed sutural fusion shortly after birth, provides an ideal model to study the biomolecular mechanisms that occur before, during, and after cranial suture fusion. 7,8 In these models, the PF cranial suture fuses between postnatal days 12 to 22 in the rat and days 25 to 45 in the mouse whereas all other sutures, including the coronal (COR) and sagittal (SAG), remain patent ( Figure 1). Using these models, our group and others have demonstrated that the dura mater directly underlying a cranial suture regulates sutural fate (ie, fusion or patency). 8 -11 In addition, we have shown that FGF-2 mRNA and protein expression in the fusing PF suture is up-regulated in the suture-associated dura mater just before and during active sutural fusion. 12,13 These findings implicate FGF biological activity in the regulation of cranial suture fusion.In this study, replication-deficient adenoviruses encoding a truncated form of FGF-R1 (AdCA...

show abstract

“…Historically, FGF2 was the first FGF ligand to be isolated from growth plate chondrocytes (Sullivan and Klagsbrun 1985). Subsequently, Fgf2 expression has also been observed in periosteal cells and in osteoblasts (Hurley et al 1994Sabbieti et al 1999). Targeted deletion of FGF2 causes a relatively subtle defect in osteoblastogenesis, leading to decreased bone growth and bone density.…”

Section: Expression Of Fgfs and Fgf Receptors In Endochondral Bonementioning

confidence: 99%

FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease

Ornitz¹,

Marie²

2002

Genes Dev.

805

638

View full text Add to dashboard Cite

Over the last decade the identification of mutations in the receptors for fibroblast growth factors (FGFs) has defined essential roles for FGF signaling in both endochondral and intramembranous bone development. FGF signaling pathways are essential for the earliest stages of limb development and throughout skeletal development. In this review, we examine the role of FGF signaling in bone development and in human genetic diseases that affect bone development. We also explore what is presently known about how FGF signaling pathways interact with other major signaling pathways that regulate chondrogenesis and osteogenesis.

show abstract

Transcriptional Regulation of the Collagenase Gene by Basic Fibroblast Growth Factor in Osteoblastic MC3T3-E1 Cells

Cited by 28 publications

References 0 publications

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

In Vivo Modulation of FGF Biological Activity Alters Cranial Suture Fate

FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease

Contact Info

Product

Resources

About