Assessing the Effect of Matrix Metalloproteinase-9 on the Growth of Mice Teeth

Author(s):  
Qingwen Ni ◽  
Shuo Chen

Dentin and bone are formed when odontoblasts and osteoblasts synthesize and secrete collagen type I-rich extracellular matrix that mineralizes in a highly controlled manner. A wide spectrum of mouse and human disorders affecting tooth and bone biomineralization shows that dentin and bone formation are under strict genetic control. Although the controlling mechanisms of dentinogenesis and osteogenesis require further study, a large body of evidence points to the importance of the matrix metalloproteinases (MMPs) participate in a wide variety of extracellular matrix degradation. Detailed knowledge of MMPs may be important for understanding the pathogenesis of tooth development. Some researchers have pointed MMP-9 is an extracelluar proteinase that is highly expressed in osteoclasts and has been postulated to play an important role in their resorptive activity. Although MMP-9 has been reported to play a role in bone resorption, the association of this enzyme during deciduous tooth resorption has not yet been clarified. Based on accumulating evidence, we hypothesized that MMP-9 should play a role in teeth attrition. In this study, we have applied NMR relaxation technique to assess age-related MMP-9 KO tooth quality in vitro by quantifying changes in dentin and pulp simultaneously. The major hypothesis in this paper was that whether noninvasive NMR relaxation time measurements could be used to characterize MMP-9 KO changes in dentin and pulp, and to predict tooth quality. Specifically, we tested that age-related MMP-9 KO tooth changes result in an alteration of the NMR spin-spin (T2) relaxation time signal due to the structural changes in the tooth matrix. This signal can be further processed to produce a T2 relaxation distribution spectrum related to dentin and pulp, and their derived parameters can be used as descriptors of age-related MMP-9 KO tooth changes. In this study, the proton liquid-like NMR spin-spin (T2) relaxation decay signal was obtained from the Carr-Purcell-Meiboom-Gill (CPMG) NMR spin echo train method [1,2], then the relaxation decay signal was converted to T2 relaxation distribution spectra describing the size domain of dentin and pulp. Therefore, we can calibrate the intensities in NMR inversion T2 relaxation distribution spectra corresponding to the amount of dentin and pulp related to the structural changes. Here, we propose an NMR calibration method “NMR standard estimation” — the ratio of the amount of pulp to the amount of dentin obtained from NMR T2 distribution spectra that can be used to measure the age-related MMP-9 KO structural changes in teeth [3]. We are cognizant of the biological and physiological variability manifest in teeth size variations, but feel that this kind of NMR standard estimation — the ratio of amount of dentin to amount of pulp from the NMR T2 inversion spectrum can be used to determine age-related MMP-9 KO structural changes in teeth and eliminate any variations in size of teeth.

Author(s):  
Qingwen Ni ◽  
Shuo Chen

It is known that NMR proton spin-spin (T2) or spin-lattice (T1) relaxation time measurements and analytical processing techniques have been used to determine microstructural characteristics of various types of fluid filled porous materials with characteristic pore sizes ranging from sub-micron to sub-millimeter. Currently this method has been developed and applied to quantify the porosity, pore size distribution and microdamage in human cortical bone [1–3]. The observed proton NMR relaxation signals are a convolution of the relaxation of fluid in the pores throughout the observed system with the longer relaxation time corresponding to larger pore sizes. Thus, regions within the bone matrix in which fluid may accumulate can effectively be treated as a “pore” and will be manifest as a change in the relaxation signal. Deconvolution of the relaxation signal can provide quantitative information about the relaxation distributions of fluid inside bone, i.e., the distribution of water within bone tissue. Since teeth are comprised of fluid-filled porous materials, and dentin is like bone, we also applied this rapid, non-destructive and non-invasive technique to detect and quantify age-related teeth structural changes particularly for both dentin and pulp based on broadline pulsed NMR.


Diabetes Care ◽  
2012 ◽  
Vol 35 (3) ◽  
pp. 513-519 ◽  
Author(s):  
G. S. Pell ◽  
A. Lin ◽  
R. M. Wellard ◽  
G. A. Werther ◽  
F. J. Cameron ◽  
...  

2019 ◽  
Vol 31 (1) ◽  
pp. 151
Author(s):  
M. Ghiringhelli ◽  
N. Verdile ◽  
T. A. L. Brevini ◽  
F. Gandolfi

Female infertility or absence of a functional uterus has a prevalence of 3 to 5% in the general human population. Nowadays most patients diagnosed with absolute uterine factor infertility remain untreatable. Moreover, the world population is aging rapidly, and as people live longer, uterus frailty increases the risk of developing age-related diseases. Whole-organ decellularization and recellularization, a novel technique within the field of regenerative medicine, could eventually provide another solution compared with the reality of gestational surrogacy. Extracellular matrix to enable recellularization has been described using different animal models, where decellularization has been performed of whole uteri. The aim of the present study was to offer a new perspective with a goat uterus as a large whole reproductive organ model. For this purpose, uteri were collected from 6 goats after slaughter and attached to the perfusion circuit. Decellularization was achieved by 2 methods of whole-uterus perfusion, namely with Triton-X100 and dimethyl sulfoxide (group 1; n=3), or with sodium deoxycholate (group 2; n=3), both compared with a control group (n=1). Morphological, immunofluorescence, real-time quantitative PCR analysis, coupled with vascular corrosion cast preparation, were used to assess protocol efficiency. Statistical analysis was carried out to identify significant differences between the 2 groups, using ANOVA and, when required, a post-hoc test (Bonferroni method). Morphological analysis showed different opacity between protocols. In both group 1 and 2, the removal of cells and cellular debris was confirmed with DNA quantification. Immunofluorescence confirmed the presence of the major extracellular matrix components, with collagen type I being the most abundant. Vascular tree network cast of the decellularized organ was successfully perfused in all the uteri. In conclusion, this preliminary study gives a new perspective in whole uterus bioengineering, utilising goats as a biological model to increase the knowledge in veterinary medicine as well as toward the in vitro and in vivo research of regenerative medicine in the field of reproduction. Research was funded by the Carraresi Foundation.


1999 ◽  
Vol 39 (7) ◽  
pp. 187-194 ◽  
Author(s):  
P. Lens ◽  
F. Vergeldt ◽  
G. Lettinga ◽  
H. Van As

The diffusive properties of mesophilic methanogenic granular sludge have been studied using diffusion analysis by relaxation time separated pulsed field gradient nuclear magnetic resonance (DARTS PFG NMR) spectroscopy. NMR measurements were performed at 22°C with 10 ml granular sludge at a magnetic field strength of 0.5 T (20 MHz resonance frequency for protons). Spin-spin relaxation (T2) time measurements indicate that three 1H populations can be distinguished in methanogenic granular sludge beds, corresponding to water in three different environments. The T2 relaxation time measurements clearly differentiate the extragranular water (T2 ≈ 1000 ms) from the water present in the granular matrix (T2 = 40-100 ms) and bacterial cell associated water (T2 = 10-15 ms). Self-diffusion coefficient measurements at 22°C of the different 1H-water populations as the tracer show that methanogenic granular sludge does not contain one unique diffusion coefficient. The observed distribution of self-diffusion coefficients varies between 1.1 × 10−9 m2/s (bacterial cell associated water) and 2.1 × 10−9 m2/s (matrix associated water).


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jannath Begum-Ali ◽  
◽  
Anna Kolesnik-Taylor ◽  
Isabel Quiroz ◽  
Luke Mason ◽  
...  

Abstract Background Sensory modulation difficulties are common in children with conditions such as Autism Spectrum Disorder (ASD) and could contribute to other social and non-social symptoms. Positing a causal role for sensory processing differences requires observing atypical sensory reactivity prior to the emergence of other symptoms, which can be achieved through prospective studies. Methods In this longitudinal study, we examined auditory repetition suppression and change detection at 5 and 10 months in infants with and without Neurofibromatosis Type 1 (NF1), a condition associated with higher likelihood of developing ASD. Results In typically developing infants, suppression to vowel repetition and enhanced responses to vowel/pitch change decreased with age over posterior regions, becoming more frontally specific; age-related change was diminished in the NF1 group. Whilst both groups detected changes in vowel and pitch, the NF1 group were largely slower to show a differentiated neural response. Auditory responses did not relate to later language, but were related to later ASD traits. Conclusions These findings represent the first demonstration of atypical brain responses to sounds in infants with NF1 and suggest they may relate to the likelihood of later ASD.


2021 ◽  
Vol 22 (5) ◽  
pp. 2685
Author(s):  
Lisa Adams ◽  
Julia Brangsch ◽  
Bernd Hamm ◽  
Marcus R. Makowski ◽  
Sarah Keller

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1046
Author(s):  
Jorge Martinez ◽  
Patricio C. Smith

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin Young Ko ◽  
Hayoung Kim ◽  
Joonyoung Jang ◽  
Jun Chang Lee ◽  
Ju Seok Ryu

AbstractAge-related weakness due to atrophy and fatty infiltration in oropharyngeal muscles may be related to dysphagia in older adults. However, little is known about changes in the oropharyngeal muscle activation pattern in older adults. This was a prospective and experimental study. Forty healthy participants (20 older [> 60 years] and 20 young [< 60 years] adults) were enrolled. Six channel surface electrodes were placed over the bilateral suprahyoid (SH), bilateral retrohyoid (RH), thyrohyoid (TH), and sternothyroid (StH) muscles. Electromyography signals were then recorded twice for each patient during swallowing of 2 cc of water, 5 cc of water, and 5 cc of a highly viscous fluid. Latency, duration, and peak amplitude were measured. The activation patterns were the same, in the order of SH, TH, and StH, in both groups. The muscle activation patterns were classified as type I and II; the type I pattern was characterized by a monophasic shape, and the type II comprised a pre-reflex phase and a main phase. The oropharyngeal muscles and SH muscles were found to develop a pre-reflex phase specifically with increasing volume and viscosity of the swallowed fluid. Type I showed a different response to the highly viscous fluid in the older group compared to that in the younger group. However, type II showed concordant changes in the groups. Therefore, healthy older people were found to compensate for swallowing with a pre-reflex phase of muscle activation in response to increased liquid volume and viscosity, to adjust for age-related muscle weakness.


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