Myocyte enhancer factor 2C : an osteoblast transcription factor identified by DMSO enhanced mineralization

Rapid mineralization of cultured osteoblasts could be a useful characteristic in stem-cell mediated therapies for fracture and other orthopaedic problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent molecule capable of simulating cell differentiation. We report that, in primary human osteoblasts, DMSO dose-dependently enhanced the expression of osteoblast differentiation markers alkaline phosphatase (ALP) activity and extracellular matrix mineralization. Furthermore, similar DMSO mediated mineralization enhancement was observed in primary osteoblast-like cells differentiated from mouse mesenchymal cells derived from fat, a promising source of starter cells for cell-based therapy. Using a convenient mouse pre-osteoblast model cell line MC3T3-E1 we further investigated this phenomenon showing that numerous osteoblast-expressed genes were elevated in response to DMSO treatment and correlated with enhanced mineralization. Myocyte enhancer factor 2c (Mef2c) was identified as the transcription factor most induced by DMSO, among numerous DMSO-induced genes, suggesting a role for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed expression of Mef2c in osteoblast-like cells in mouse mandible, cortical and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted in defective osteoblast differentiation, decreased ALP activity and matrix mineralization and knockdown of osteoblast specific gene expression, including osteocalcin and bone sialoprotein. Flow on knockdown of bone specific transcription factors, Runx2 and osterix by shRNAi knockdown of Mef2c suggests that Mef2c lies upstream of these two important factors in the cascade of gene expression in osteoblasts.

Supportive-expressive group therapy for women with metastatic breast cancer: Improving access for Australian women through use of teleconference

While supportive-expressive group therapy (SEGT) has been found to be effective in significantly reducing distress associated with life-threatening illness, the challenge in Australia is to develop a means of providing supportive interventions to rural women who may be isolated both by the experience of illness and by geographical location. In this study an adaptation of SEGT was provided to women with metastatic breast cancer (n =21), who attended face-to-face or by telephone conference call. Participants showed significant gains on standardised measures of well-being, including a reduction in negative affect and an increase in positive affect, over a 12-month period. A reduction in intrusive and avoidant stress symptoms was also observed over 12 months; however, this difference was not significant. These outcomes suggest that SEGT, delivered in an innovative way within a community setting, may be an effective means of moderating the adverse effects of a diagnosis of metastatic breast cancer while improving access to supportive care for rural women. These results are considered exploratory, as the study did not include a matched control group.