Nmp4/CIZ regulation of matrix metalloproteinase 13 (MMP-13) response to parathyroid hormone in osteoblasts

Parathyroid hormone (PTH) regulation of matrix metalloproteinase-13 ( MMP-13) expression in osteoblasts contributes to normal bone turnover. The PTH response region of the rat MMP-13 gene spans nucleotides (nt) −148 to −38 and supports binding of numerous transcription factors, including Runx2, necessary for osteoblast differentiation, c-Fos/c-Jun, and Ets-1. These trans-acting proteins mediate hormone induction via incompletely defined combinatorial interactions. Within this region, adjacent to the distal Runx2 site, is a homopolymeric(dA:dT) element (−119/−110 nt) that conforms to the consensus site for the novel transcription factor nuclear matrix protein-4/cas interacting zinc finger protein (Nmp4/CIZ). This protein regulates bone cell expression of type I collagen and suppresses BMP2-enhanced osteoblast differentiation. The aim of this study was to determine whether Nmp4/CIZ contributes to MMP-13 basal transcription and PTH responsiveness in osteoblasts. Electrophoretic mobility shift analysis confirms Nmp4/CIZ binding within the MMP-13 PTH response region. Mutation of the Nmp4/CIZ element decreases basal activity of an MMP-13 promoter-reporter construct containing the first 1329 nt of the 5′-regulatory region, and overexpression of Nmp4/CIZ protein enhances the activity of the wild-type promoter. The same mutation of the homopolymeric(dA:dT) element enhances the MMP-13 response to PTH and PGE2. Overexpression of Nmp4/CIZ diminishes hormone induction. Mutation of both the homopolymeric(dA:dT) element and the adjacent Runx2 site further augments the PTH response. On the basis of these data and previous studies, we propose that Nmp4/CIZ is a component of a multiprotein assemblage or enhanceosome within the MMP-13 PTH response region and that, within this context, Nmp4/CIZ promotes both basal expression and hormonal synergy.

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Reciprocal Modulation of Matrix Metalloproteinase-13 and Type I Collagen Genes in Rat Hepatic Stellate Cells

American Journal Of Pathology ◽

10.1016/s0002-9440(10)64312-x ◽

2003 ◽

Vol 162 (6) ◽

pp. 1771-1780 ◽

Cited By ~ 37

Author(s):

Benjamin Schaefer ◽

Ana María Rivas-Estilla ◽

Noemí Meraz-Cruz ◽

Miguel Arturo Reyes-Romero ◽

Zamira H. Hernández-Nazara ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Hepatic Stellate Cells ◽

Type I Collagen ◽

Stellate Cells ◽

Type I ◽

Matrix Metalloproteinase 13 ◽

Collagen Genes

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Type I collagen from sea cucumber (Stichopus japonicus) and the role of matrix metalloproteinase-2 in autolysis

Food Bioscience ◽

10.1016/j.fbio.2021.100959 ◽

2021 ◽

Vol 41 ◽

pp. 100959

Author(s):

Long-Jie Yan ◽

Le-Chang Sun ◽

Kai-Yuan Cao ◽

Yu-Lei Chen ◽

Ling-Jing Zhang ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Sea Cucumber ◽

Type I Collagen ◽

Matrix Metalloproteinase 2 ◽

Type I ◽

Stichopus Japonicus

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Effects of hydroxycamptothecin on the expression of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of MMP-1, and type I collagen in rats with pulmonary fibrosis

Genetics and Molecular Research ◽

10.4238/2015.may.4.21 ◽

2015 ◽

Vol 14 (2) ◽

pp. 4625-4632 ◽

Cited By ~ 3

Author(s):

G.-X. Hu ◽

S.-T. Yao ◽

L.-H. Zeng ◽

Y.-Z. Peng ◽

J. Zheng

Keyword(s):

Pulmonary Fibrosis ◽

Matrix Metalloproteinase ◽

Type I Collagen ◽

Type I ◽

Tissue Inhibitor ◽

Matrix Metalloproteinase 1

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A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis

Arthritis Research & Therapy ◽

10.1186/s13075-021-02610-y ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Louie C. Alexander ◽

Grant McHorse ◽

Janet L. Huebner ◽

Anne-Christine Bay-Jensen ◽

Morten A. Karsdal ◽

...

Keyword(s):

Synovial Fluid ◽

Matrix Metalloproteinase ◽

Type I Collagen ◽

Joint Inflammation ◽

Cartilage Degradation ◽

Womac Pain ◽

Type Iii Collagen ◽

Type I ◽

Radiographic Imaging ◽

Type Iii

Abstract Objective To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. Methods Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). Results BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. Conclusions To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

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The Effect of the Combination of Vitamin K2 and Genistein, Coumestrol and Daidzein on the Osteoblast Differentiation and Bone Matrix Formation

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2016.10.2.474 ◽

2016 ◽

Vol 10 (2) ◽

pp. 12-19

Author(s):

Sahar S. Karieb ◽

Mohammed M. Jawad ◽

Hanady S. Al-Shmgani ◽

Zahraa H.M. Kadri

Keyword(s):

Bone Formation ◽

Osteoblast Differentiation ◽

Nuclear Factor Kappa B ◽

Type I Collagen ◽

Bone Mineralization ◽

Bone Matrix ◽

Vitamin K2 ◽

Type I ◽

Nuclear Factor ◽

Effective Factor

Multiple studies have been reported the stimulatory effect of the combinations of nutrients factors on bone formation. One such factor is vitamin K2 which can be associated with bone protective activities. The effect of vitamin K2 alone and in combination with genistein, coumestrol and daidzein on osteoblast differentiation and mineralization were tested. Significantly, vitamin K2 increased bone mineralization in combination with genistein (10-5M), coumestrol (10-7M) and daidzein (10-5M). However, there is no additive effect of this vitamin on alkaline phosphatase (ALP) levels in osteoblasts. By contrast, vitamin K2 enhanced the stimulatory effect of type I collagen and osteocalcin expression. Vitamin K2 alone increased RUNX and OSX expression while there is no synergistic effect with tested compound; this vitamin also did not modulate nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) ratio expression. These results suggested that vitamin K2 can be more effective factor in the presence of phytoestrogens on the improvement of bone formation after menopause.

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Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia

Neurology Genetics ◽

10.1212/nxg.0000000000000508 ◽

2020 ◽

Vol 6 (5) ◽

pp. e508

Author(s):

Man-Hung Eric Tang ◽

Joseph P.M. Blair ◽

Cecilie Liv Bager ◽

Anne-Christine Bay-Jensen ◽

Kim Henriksen ◽

...

Keyword(s):

Cognitive Impairment ◽

Matrix Metalloproteinase ◽

Gene Cluster ◽

Type I Collagen ◽

Early Death ◽

Collagen Metabolism ◽

Type I ◽

Age Related ◽

Genome Wide ◽

A Genome

ObjectiveDysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase–degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulation, we have performed a genome-wide screening of the genetic factors related to type I collagen turnover.MethodsPatient registry data and genotypes have been collected for a total of 4,981 Danish postmenopausal women. Genome-wide association with serum levels of C1M was assessed and phenotype-genotype association analysis performed.ResultsTwenty-two genome-wide significant variants associated with C1M were identified in the APOE-C1/TOMM40 gene cluster. The APOE-C1/TOMM40 gene cluster is associated with hyperlipidemia and cognitive disorders, and we further found that C1M levels correlated with tau degradation markers and were decreased in women with preclinical cognitive impairment.ConclusionsOur study provides elements for better understanding the role of the collagen metabolism in the onset of cognitive impairment.

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Carboxyterminal telopeptide of type I collagen, ICTP, as a marker of matrix degradation in neonatal mouse calvarial bones, in vitro

Bioscience Reports ◽

10.1007/bf01121504 ◽

1992 ◽

Vol 12 (5) ◽

pp. 407-411 ◽

Cited By ~ 3

Author(s):

Östen Ljunggren ◽

Sverker Ljunghall

Keyword(s):

Parathyroid Hormone ◽

Bone Resorption ◽

Type I Collagen ◽

Bone Matrix ◽

Neonatal Mouse ◽

Type I ◽

Matrix Degradation ◽

Dose Responses ◽

Carboxyterminal Telopeptide

Bone resorption, in vitro, is often measured as the release of prelabelled45Ca from neonatal mouse calvarial bones, or from fetal rat long bones. In this report we describe a technique to measure the breakdown of bone-matrix, in vitro. We also describe a new way to dissect neonatal mouse calvarial bones, in order to obtain large amounts of bone samples. Twelve bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 culture medium in serum-free conditions in 0.5 cm2 multiwell culture dishes. Matrix degradation after treatment with parathyroid hormone was assessed by measuring the amount of carboxyterminal telopeptide of type I collagen (ICTP) by RIA. The data on matrix degradation was compared to the release of prelabelled45Ca from neonatal mouse calvarial bones. We found that the dose-responses for parathyroid hormone-induced release of prelabelled45Ca and ICTP were identical. In conclusion: RIA-analysis of the ICTP-release is an easy and accurate method to measure degradation of bone-matrix, in vitro. Furthermore, the new dissection technique, described in this report, makes it easy to obtain large amounts of bone samples and thus to perform extensive experiments, e.g. dose-responses for agents that enhance bone resorption.

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