Chronic Pain in the Lower Extremities and Low Back is Associated With Recurrent Falls in Community-Dwelling Japanese People Aged 40-74 Years.

OBJECTIVE: To determine the longitudinal association between chronic pain in the lower extremities and low back and the odds of recurrent falls in middle-aged and older people. DESIGN: A cohort study. SETTING: Communities in Japan. PARTICIPANTS: Participants were 7540 community-dwelling volunteers aged 40-74 years (N=7540). The baseline survey was a self-administered questionnaire conducted between 2011-2013. Predictors were presence of chronic pain in the knee, foot or ankle, and low back, with the degree of pain categorized as none, very mild/mild, moderate, or severe/very severe. Covariates in the multivariate model of chronic pain in a site were demographics, body mass index, physical activity level, disease history, and chronic pain in the other 2 sites. Logistic regression analysis was used to calculate odds ratios (ORs). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Recurrent falls in the year before the 5-year follow-up survey. RESULTS: Mean participant age was 60.2 years. Higher degrees of chronic pain were associated with higher odds of recurrent falls for the knee (P=.0002) with a higher OR of 1.48 (95% CI: 1.11-1.97), for the foot or ankle (P=.0001) with a higher OR of 1.97 (95% CI: 1.36-2.86), and for the low back (P=.0470) with a higher OR of 1.45 (95% CI: 1.09-1.91) in those with any degree of pain relative to those without pain. Higher degrees of chronic knee pain were associated with higher odds of recurrent falls in women (P=.0005), but not in men (P=.0813). Meanwhile, higher degrees of chronic low back pain were associated with the odds of recurrent falls in men (P=.0065), but not in women (P=.8735). CONCLUSIONS: Chronic pain in the knee, foot or ankle, and lower back was independently and dose-dependently associated with a higher risk of recurrent falls. A marked sex-dependent difference was also noted in the association.

Mechanical strain increases expression of type XII collagen in murine osteoblastic MC3T3-E1 cells.

In adult mouse, the mRNA corresponding to the alpha1 chain of type XII collagen (alpha 1(XII)) is predominantly detected in the bone. Additionally, murine osteoblastic cells, MC3T3-E1, increased the mRNA level of alpha 1(XII) response to the mechanical strain in the stretch culture system. Cyclic stretch stress resulted in a threefold increase in mRNA level of alpha 1(XII) as compared to the control experiment in MC3T3-E1. Transient transfection assays employing a reporter construct, together with site-directed mutagenesis studies, suggested that the AP-1 binding site in the first exon of mouse alpha 1(XII) gene is important for stretch stress-mediated upregulation of alpha 1(XII) expression. Electrophoretic mobility shift assay and associated antibody supershift experiments showed that stretch stress promotes the binding of c-Jun and JunD. Further chromatin immunoprecipitation experiments confirmed the participation of these transcription factors in the region. Also, the exogenous induction of the dominant negative form of c-Jun canceled the effect of stretch stress on the stimulation of the alpha 1(XII) gene. Here, we reported a potential responsive element to the stretch stress in mouse alpha 1(XII) gene. These data will provide new information on the mechanical strain-mediated transcriptional control of alpha 1(XII)-mediated fibrillogenesis in the bone.

Regulation of class II beta-tubulin expression by tumor suppressor p53 protein in mouse melanoma cells in response to Vinca alkaloid.

The continuous exposure of antimicrotubule drugs to tumors often results in the emergence of drug-resistant tumor cells with altered expression of several beta-tubulin isotypes. We found that Vinca alkaloid enhanced expression of class II beta-tubulin isotype (mTUBB2) in mouse B16F10 melanoma cells via alteration of the tumor suppressor p53 protein. Vincristine treatment stimulated an increase in mTUBB2 mRNA expression and promoted accumulation of this isotype around the nuclei. Transient transfection assays employing a reporter construct, together with site-directed mutagenesis studies, suggested that the p53-binding site found in the first intron was a critical region for mTUBB2 expression. Electrophoretic mobility shift assay and associated antibody supershift experiments showed that vincristine promoted release of p53 protein from the binding site. In addition, exogenous induction of TAp63gamma (p51A), a homologue of p53, canceled the effect of vincristine on mTUBB2 expression. These results suggest that p53 protein may function as a suppressor of mTUBB2 expression and vincristine-mediated inhibition of p53 binding results in enhanced mTUBB2 expression. This phenomenon could be related with the emergence of drug-resistant tumor cells induced by Vinca alkaloid and may participate in determining the fate of these cells.