Regulation of expression of collagenase-3 in normal, differentiating rat osteoblasts

Winchester, Sandra K.; Bloch, Sharon; Fiacco, Gerald J.; Partridge, Nicola C.

doi:10.1002/(sici)1097-4652(199912)181:3<479::aid-jcp12>3.0.co;2-d

Cited by 46 publications

(33 citation statements)

References 57 publications

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“…Located Upstream of the TSS-Mmp13 transcription is up-regulated during early precursor cell differentiation into mature, mineralizing osteoblasts (14) and modulated by a myriad of regulatory factors that include 1,25(OH) 2 D 3 (23). These conclusions are confirmed by the observations in Fig.…”

Section: Mmp13 Is Regulated By Three Distinct Distal Enhancerssupporting

confidence: 66%

“…In studies of PTH action, Mmp13 was found to be regulated by Runt-related transcription factor-2 (RUNX2) through a Runt binding domain DNA sequence located near an AP-1 site adjacent to the Mmp13 promoter (9). Additional studies revealed that both PKC and PKA signaling pathways are active at the AP-1 and RUNX2 binding sites, respectively (14,15). This ongoing work has focused much of the molecular investigation of Mmp13 regulation by PTH and other hormones on these specific promoter proximal sites in bone cells.…”

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confidence: 99%

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Selective Distal Enhancer Control of the Mmp13 Gene Identified through Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Genomic Deletions

Meyer

Benkusky

Pike

2015

Journal of Biological Chemistry

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Background:Mmp13 is vital to bone homeostasis and controlled by a plethora of stimuli. Results: Mmp13 is modulated by distinct distal enhancers for basal (Ϫ30 kb) and vitamin D regulation (Ϫ10 kb). Conclusion: Enhancer deletions lead to altered transcription factor occupancy and expression for Mmp13. Significance: Specific CRISPR deletions reveal the repressive secondary effect of VDR, coordinated multi-enhancer gene control, and distal basal regulation of Mmp13.

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Section: Mmp13 Is Regulated By Three Distinct Distal Enhancerssupporting

confidence: 66%

mentioning

confidence: 99%

Selective Distal Enhancer Control of the Mmp13 Gene Identified through Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Genomic Deletions

Meyer

Benkusky

Pike

2015

Journal of Biological Chemistry

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“…In bone formation, mineral deposition occurs in the final stage of osteoblast differentiation and is associated with maximal osteoblastic expression of osteocalcin and MMP-13 (20,21,53). Several in vitro studies have indicated that the clonal cell line, C2C12, when cultured under appropriate conditions, might give rise to cells of the osteoblastic lineage with the addition of BMP-2 (50).…”

Section: Discussionmentioning

confidence: 99%

“…Various bone-resorbing agents, such as PTH, increase collagen degradation by increasing MMP production and inhibiting collagen synthesis (19). Similar to osteocalcin, MMP-13 gene expression increases during osteoblastic differentiation (20,21) and is transcriptionally regulated by Runx2, a runt domain-binding transcription factor found in osteoblasts, during this process.…”

Section: Introductionmentioning

confidence: 99%

Regulation of matrix metalloproteinase-13 and tissue inhibitor of matrix metalloproteinase-1 gene expression by WNT3A and bone morphogenetic protein-2 in osteoblastic differentiation

Nakashima

Tamura²

2006

Front Biosci

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“…For example, PTH stimulates collagenase-3 gene expression in osteoblastic cells and requires the activator protein-1 (AP-1) and RD binding regions found just upstream of the collagenase-3 transcriptional start site (52,53). Similar to OC, collagenase-3 gene expression increases during differentiation (6,54) and is transcriptionally regulated during this process (6). Given that collagenase-3 and OC are expressed during similar periods of osteoblast differentiation and that expression of both genes is regulated by RUNX2/Cbfa1, it seems reasonable to hypothesize that collagenase-3, like OC, is also regulated by integrin interaction with the extracellular matrix.…”

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confidence: 99%

Regulation of Collagenase-3 and Osteocalcin Gene Expression by Collagen and Osteopontin in Differentiating MC3T3-E1 Cells

DʼAlonzo

Kowalski

Denhardt

et al. 2002

Journal of Biological Chemistry

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Both collagenase-3 and osteocalcin mRNAs are expressed maximally during the later stages of osteoblast differentiation. Here, we demonstrate that collagenase-3 mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence of ascorbic acid, is inhibited in the presence of the collagen synthesis inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the absence of ascorbic acid. Transient transfection studies show that collagenase-3 promoter activity increases during cell differentiation and requires the presence of ascorbic acid. Additionally, we show that, in differentiating MC3T3-E1 cells, collagenase-3 gene expression increases in the presence of an anti-osteopontin monoclonal antibody that binds near the RGD motif of this protein, whereas osteocalcin expression is inhibited. Furthermore, an RGD peptidomimetic compound, designed to block interaction of ligands to the ␣ v integrin subunit, increases osteocalcin expression and inhibits collagenase-3 expression, suggesting that the RGD peptidomimetic initiates certain ␣ v integrin signaling in osteoblastic cells. Overall, these studies demonstrate that stimulation of collagenase-3 expression during osteoblast differentiation requires synthesis of a collagenous matrix and that osteopontin and ␣ v integrins exert divergent regulation of collagenase-3 and osteocalcin expression during osteoblast differentiation.When primary or clonal osteoblastic cells, such as MC3T3-E1 cells, are cultured with ␤-glycerophosphate (␤-gly) 1 and ascorbic acid (AA), the cells undergo a differentiation process and eventually produce bone nodules resembling woven bone in vitro (1-4). Mineral deposition occurs in the final stages of osteoblast differentiation and is associated with maximal osteoblastic expression of osteocalcin and collagenase-3 (5-7). The mechanisms controlling osteoblast differentiation are unclear, but research suggests that a reciprocal interaction exists between the osteoblast and the surrounding extracellular matrix. For example, when osteoblasts or osteoblast-like cells are grown on plates pre-coated with collagen, they exhibit early signs of osteoblast maturation and osteoblastic gene expression (8 -12). Further accumulating data suggest that the extracellular matrix mediates many effects through activation of integrin signaling pathways in osteoblasts (12-14). Osteoblasts and osteoblast-like cells have been reported to express a wide variety of integrin receptor subunits, including ␣ 1 , ␣ 2 , ␣ 3 , ␣ 4 , ␣ 5 , ␣ v , ␤ 1 , and ␤ 3 (15-17).Osteocalcin (OC), or bone gla protein, is a calcium-binding protein found in bone extracellular matrix and expressed by osteoblasts, odontoblasts, and hypertrophic chondrocytes (reviewed in Ref. 18). It has an affinity for hydroxyapatite, suggesting a role in the regulation of mineralization. In fact, OCnull mutant mice exhibit increased bone density (19), although defects in mineralization have been detected (20). Recent evidence suggests that the up-regulation of OC late in osteoblast diff...

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Regulation of expression of collagenase-3 in normal, differentiating rat osteoblasts

Cited by 46 publications

References 57 publications

Selective Distal Enhancer Control of the Mmp13 Gene Identified through Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Genomic Deletions

Selective Distal Enhancer Control of the Mmp13 Gene Identified through Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Genomic Deletions

Regulation of matrix metalloproteinase-13 and tissue inhibitor of matrix metalloproteinase-1 gene expression by WNT3A and bone morphogenetic protein-2 in osteoblastic differentiation

Regulation of Collagenase-3 and Osteocalcin Gene Expression by Collagen and Osteopontin in Differentiating MC3T3-E1 Cells

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