Connexins and pannexins in the skeleton: gap junctions, hemichannels and more

Regulation of bone homeostasis depends on the concerted actions of bone-forming osteoblasts and bone-resorbing osteoclasts, controlled by osteocytes, cells derived from osteoblasts surrounded by bone matrix. The control of differentiation, viability and function of bone cells relies on the presence of connexins. Connexin43 regulates the expression of genes required for osteoblast and osteoclast differentiation directly or by changing the levels of osteocytic genes, and connexin45 may oppose connexin43 actions in osteoblastic cells. Connexin37 is required for osteoclast differentiation and its deletion results in increased bone mass. Less is known on the role of connexins in cartilage, ligaments and tendons. Connexin43, connexin45, connexin32, connexin46 and connexin29 are expressed in chondrocytes, while connexin43 and connexin32 are expressed in ligaments and tendons. Similarly, although the expression of pannexin1, pannexin2 and pannexin3 has been demonstrated in bone and cartilage cells, their function in these tissues is not fully understood

Interaction of connexin43 and protein kinase C-delta during FGF2 signaling

<p>Abstract</p> <p>Background</p> <p>We have recently demonstrated that modulation of the gap junction protein, connexin43, can affect the response of osteoblasts to fibroblast growth factor 2 in a protein kinase C-delta-dependent manner. Others have shown that the C-terminal tail of connexin43 serves as a docking platform for signaling complexes. It is unknown whether protein kinase C-delta can physically interact with connexin43.</p> <p>Results</p> <p>In the present study, we investigate by immunofluorescent co-detection and biochemical examination the interaction between Cx43 and protein kinase C-delta. We establish that protein kinase C-delta physically interacts with connexin43 during fibroblast growth factor 2 signaling, and that protein kinase C delta preferentially co-precipitates phosphorylated connexin43. Further, we show by pull down assay that protein kinase C-delta associates with the C-terminal tail of connexin43.</p> <p>Conclusions</p> <p>Connexin43 can serve as a direct docking platform for the recruitment of protein kinase C-delta in order to affect fibroblast growth factor 2 signaling in osteoblasts. These data expand the list of signal molecules that assemble on the connexin43 C-terminal tail and provide a critical context to understand how gap junctions modify signal transduction cascades in order to impact cell function.</p

The relationship between obesity and cancer

Obesity is an urgent and growing global health problem. Among other co-morbidities, obesity is associated with a significantly increased risk of developing many cancers. The epidemiological evidence linking obesity and cancer has ignited multiple studies trying to understand how obesity contributes to cancer risk. Although mechanisms underlying the obesity-cancer link are becoming increasingly clearer, they are very complex and still under intense investigation. Strategies that prevent and/or reverse obesity may also be useful for reducing the progression of cancer. Recent interests are focused towards brown fat as a primary target to combat obesity. In this review, we integrate the classic understandings of the mechanistic role of obesity in cancer to the studies which suggest a beneficial role of brown fat to humans

Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice

Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group’s exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear. Skeletal muscle exhibited structural and functional adaptations to exercise training, as revealed by electron microscopy, OXPHOS assays, respirometry, and muscle protein biomarkers. Transcriptomics analysis of gastrocnemius muscle combined with liver and serum metabolomics unveiled an age-dependent metabolic remodeling in response to exercise training. These results support a tailored exercise prescription approach aimed at improving health and ameliorating age-associated loss of muscle strength and function in the elderly.This work was supported by funding from the Intramural Research Program of the National Institute on Aging/NIH. Work in JMV laboratory was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) grant BFU2015-64630-R, Ministerio de Ciencia, Innovación y Universidades (MICIU) grant RTI2018-100695-B-I00, Spanish Junta de Andalucía grants P18-RT-4264, 1263735-R and BIO-276, the FEDER Funding Program from the European Union, and Universidad de Córdoba. MCR was supported by a FPU fellowship from the Spanish Ministerio de Educación, Cultura y Deporte (reference FPU14/06308). SRL held a FPI predoctoral contract funded by MINECO (reference BES-2016-078229).Peer reviewe