High‐fat high‐sucrose diet leads to dynamic structural and inflammatory alterations in the rat vastus lateralis muscle

The influence of obesity on muscle integrity is not well understood. The purpose of this study was to quantify structural and molecular changes in the rat vastus lateralis (VL) muscle as a function of a 12‐week obesity induction period and a subsequent adaptation period (additional 16‐weeks). Male Sprague–Dawley rats consumed a high‐fat, high‐sucrose (DIO, n = 40) diet, or a chow control‐diet (n = 14). At 12‐weeks, DIO rats were grouped as prone (DIO‐P, top 33% of weight change) or resistant (DIO‐R, bottom 33%). Animals were euthanized at 12‐ or 28‐weeks on the diet. At sacrifice, body composition was determined and VL muscles were collected. Intramuscular fat, fibrosis, and CD68+ cells were quantified histologically and relevant molecular markers were evaluated using RT‐qPCR. At 12‐ and 28‐weeks post‐obesity induction, DIO‐P rats had more mass and body fat than DIO‐R and chow rats (p < 0.05). DIO‐P and DIO‐R rats had similar losses in muscle mass, which were greater than those in chow rats (p < 0.05). mRNA levels for MAFbx/atrogin‐1 were reduced in DIO‐P and DIO‐R rats at 12‐ and 28‐weeks compared to chow rats (p < 0.05), while expression of MuRF1 was similar to chow values. DIO‐P rats demonstrated increased mRNA levels for pro‐inflammatory mediators, inflammatory cells, and fibrosis compared to DIO‐R and chow animals, despite having similar levels of intramuscular fat. The down‐regulation of MAFbx/atrogin‐1 may suggest onset of degenerative changes in VL muscle integrity of obese rats. DIO‐R animals exhibited fewer inflammatory changes compared to DIO‐P animals, suggesting a protective effect of obesity resistance on local inflammation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2069–2078, 2016.     

The Actin‐Binding Protein Cofilin and Its Interaction With Cortactin Are Required for Podosome Patterning in Osteoclasts and Bone Resorption In Vivo and In Vitro

The adhesion of osteoclasts (OCs) to bone and bone resorption require the assembly of specific F‐actin adhesion structures, the podosomes, and their dense packing into a sealing zone. The OC‐specific formation of the sealing zone requires the interaction of microtubule (MT) + ends with podosomes. Here, we deleted cofilin, a cortactin (CTTN)‐ and actin‐binding protein highly expressed in OCs, to determine if it acts downstream of the MT‐CTTN axis to regulate actin polymerization in podosomes. Conditional deletion of cofilin in OCs in mice, driven by the cathepsin K promoter (Ctsk‐Cre), impaired bone resorption in vivo, increasing bone density. In vitro, OCs were not able to organize podosomes into peripheral belts. The MT network was disorganized, MT stability was decreased, and cell migration impaired. Active cofilin stabilizes MTs and allows podosome belt formation, whereas MT disruption deactivates cofilin via phosphorylation. Cofilin interacts with CTTN in podosomes and phosphorylation of either protein disrupts this interaction, which is critical for belt stabilization and for the maintenance of MT dynamic instability. Accordingly, active cofilin was required to rescue the OC cytoskeletal phenotype in vitro. These findings suggest that the patterning of podosomes into a sealing zone involves the dynamic interaction between cofilin, CTTN, and the MTs + ends. This interaction is critical for the functional organization of OCs and for bone resorption. © 2016 American Society for Bone and Mineral Research.     

Findings from a mixed-methods study of an interprofessional faculty development program

Forty faculty members from eight schools participated in a year-long National Faculty Development Program (NFDP) conducted in 2012–2013, aimed at developing faculty knowledge and skills for interprofessional education (IPE). The NFDP included two live conferences. Between conferences, faculty teams implemented self-selected IPE projects at their home institutions and participated in coaching and peer-support conference calls. This paper describes program outcomes. A mixed methods approach was adopted. Data were gathered through online surveys and semi-structured interviews. The study explored whether faculty were satisfied with the program, believed the program was effective in developing knowledge and skills in designing, implementing, and evaluating IPE, and planned to continue newly-implemented IPE and faculty development (FD). Peer support and networking were two of the greatest perceived benefits. Further, this multi-institutional program appears to have facilitated early organizational change by bringing greater contextual understanding to assumptions made at the local level that in turn could influence hidden curricula and networking. These findings may guide program planning for future FD to support IPE.