👤 Christopher J Lux

Histone Lys-specific demethylases (KDMs) play a key role in many biological processes through epigenetic mechanisms. However, the role of KDMs in inflammatory responses to oral bacterial infection is poorly understood. Here, we show a novel regulatory role of KDM3C in inflammatory responses to oral bacterial infection. KDM3C expression is transiently suppressed in human and mouse macrophages exposed to LPS from Show less

One of the most common side effects of orthodontic treatment is root resorption on the pressure side of tooth movement. This is usually repaired by cementoblasts, but 1-5 % of patients eventually experiences a marked reduction in root length because no repair has occurred. The reason why cementoblasts should lose their repair function in such cases is not well understood. There is evidence from genome-wide expression analysis (Illumina HumanHT-12 v4 Expression BeadChip Kit; > 30,000 genes) that apoptotic processes are upregulated after the compression of cementoblasts, which is particularly true of the pro-apoptotic gene AXUD1. Human primary cementoblasts (HPCBs) from two individuals were subjected to compressive loading at 30 g/cm(2) for 1/6/10 h. The cells were then evaluated for apoptosis by flow cytometry, for mRNA expression of putative genes (AXUD1, AXIN1, AXIN2) by quantitative PCR, and for involvement of c-Jun-N-terminal kinases (JNKs) in the regulation of AXUD1 via western blotting. In addition, platelet-derived growth factor receptor-β (PDGFRβ) was selectively inhibited by SU16f to analyze the effect of PDGFRβ-dependent signal transduction on AXUD1 and AXIN1 expression. The percentage of apoptotic HPCBs rose after only 6 h of compressive loading, and 18-20 % of cells were apoptotic after 10 h. Microarray data revealed significant upregulation of the pro-apoptotic gene AXUD1 after 6 h and quantitative PCR significant AXUD1 upregulation after 6 and 10 h of compression. AXIN1 and AXIN2 expression in HPCBs was significantly increased after compressive loading. Our tests also revealed that PDGFRβ signaling inhibition by SU16f augmented the expression of AXIN1 and AXUD1 in HPCBs under compression. Increased apoptosis of compressed HPCBs might help explain why cementoblasts, rather than invariably repairing all cases of root resorption, sometimes allow the original root length to shorten. The pathway hypothesized to lead to cementoblast apoptosis involves PDGF signaling, with this signal transduction's inhibition augmenting the expression of pro-apoptotic genes. Thus activating PDGF signaling may modify the signaling pathway for the apoptosis of cementoblasts, which would reveal a protective role of PDGF for these cells. Further studies are needed to develop strategies of treatment capable of minimizing root resorption. Show less

Apolipoproteins have recently been implicated in the etiology of Alzheimer's disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals. Show less