ABSTRACT
We previously reported that the increased expression of Dickkopf-related protein 1 (DKK1) is positively related to vascular endothelial growth factor in the synovial fluid from patients with temporomandibular joint disorders (TMDs). DKK1 is involved in angiogenic activities in the TMD synovium in vitro, but the expression of DKK1 after treatment of TMD-osteoarthritis (TMD-OA) with hyaluronic acid (HA) remains unknown. In this study, we assessed the expression of DKK1 in the synovial fluid of TMD-OA patients before and after treatment with HA via enzyme-linked immunosorbent assay. We also investigated the role of DKK1 in TMD-OA via immunohistochemical staining. The relationship between the expression of DKK1 and the clinicopathological characteristics was determined by Pearson analysis. The results showed that the expression of DKK1 was significantly decreased after treatment with HA. Correlation analyses indicated that the expression of DKK1 in the TMD-OA samples was closely correlated with mouth opening and pain. These findings suggest that DKK1 could play an important role in the pathogenesis and treatment of TMD. Reduction of the pain by HA treatment may be correlated with the decreased expression of DKK1.
Subject(s)
Hyaluronic Acid/therapeutic use , Intercellular Signaling Peptides and Proteins/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Temporomandibular Joint Disorders/drug therapy , Temporomandibular Joint Disorders/metabolism , Adolescent , Adult , Female , Humans , Male , Middle Aged , Synovial Fluid/drug effects , Synovial Fluid/metabolism , Synovial Membrane/drug effects , Synovial Membrane/metabolism , Young AdultABSTRACT
Haploinsufficiency of the runt-related transcription factor 2 (Runx2) gene is widely known to be responsible for cleidocranial dysplasia (CCD). To date, more than 190 mutations in Runx2 gene have been reported to be related to CCD. In this study, a novel mutation of Runx2 gene was observed in a female with CCD. Genomic DNA was extracted from peripheral venous blood of the proband and eleven members of her family. Genetic testing on these twelve people identified a novel missense mutation (c.895 T>C, Y299H) in exon 5 of the RUNX2 gene in the proband. This mutation results in an amino acid change at codon 895 (P.Tyr 299 His.) from a tryptophan codon (TAT) to a histidine codon (CAT). Our finding may further extend the known mutation spectrum of the RUNX2 gene, and facilitate prenatal genetic diagnosis of CCD in the future.
Subject(s)
Cleidocranial Dysplasia/genetics , Core Binding Factor Alpha 1 Subunit/genetics , Mutation, Missense , Sequence Analysis, DNA/methods , Adult , Amino Acid Substitution , Exons , Female , Genetic Predisposition to Disease , Histidine/genetics , Humans , Pedigree , Tryptophan/geneticsABSTRACT
Haploinsuffieiency of the runt-related transcription factor 2 (Runx2) gene is widely known to be responsible for cleidocranial dysplasia (CCD).To date,more than 190 mutations in Runx2 gene have been reported to be related to CCD.In this study,a novel mutation of Runx2 gene was observed in a female with CCD.Genomic DNA was extracted from peripheral venous blood of the proband and eleven members of her family.Genetic testing on these twelve people identified a novel missense mutation (c.895T＞C,Y299H) in exon 5 of the RUNX2 gene in the proband.This mutation results in an amino acid change at codon 895 (P.Tyr 299 His.) from a tryptophan codon (TAT) to a histidine codon (CAT).Our finding may further extend the known mutation spectrum of the RUNX2 gene,and facilitate prenatal genetic diagnosis of CCD in the future.
ABSTRACT
In temporomandibular disorders (TMD), pain takes place when neuropeptides stimulate synovial tissue to produce several cytokines such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, which activate neurons and glia of synovial membrane at the bilaminar regions of temporomandibular joint (TMJ). It has been reported that, after neurogenic differentiation, the synovial mesenchymal stem cells (SMSCs), deriving from TMJ, possess the same cytological features as the neuronal cells. This study examined the ability of substance P (SP) and calcitonin gene-related peptide (CGRP) to stimulate SMSCs and neurogenic SMSCs secreting inflammatory cytokines during TMD, evaluated the mutual effects of inflammatory cytokines and neuropeptides and tested the analgesic effect of hyaluronic acid (HA). The levels of IL-1ß, IL-6 and TNF-α in SMSCs and neurogenic SMSCs in the presence of neuropeptides were measured by ELISA. SP and CGRP produced by SMSCs and neurogenic SMSCs were determined by RT-PCR and Western blotting. The results showed that the expression of SP and CGRP was significantly enhanced in the neurogenic SMSCs in response to IL-1ß, IL-6 and TNF-α, and the effect was remarkably inhibited by HA. IL-1ß, IL-6 and TNF-α, in return, could be enhanced in the neurogenic SMSCs upon stimulation by SP and CGRP. Neuropeptides and inflammatory cytokines might work mutually on the TMD pain. The HA-mediated analgesic effect may be implicated in the inhibition of SP and CGRP expression in neurogenic SMSCs.
