Connexins and Pannexins in Bone and Skeletal Muscle

Plotkin, Lilian I.; Davis, Hannah M.; Cisterna, Bruno A.; Sáez, Juan C.

doi:10.1007/s11914-017-0374-z

Cited by 44 publications

(34 citation statements)

References 104 publications

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“…Connexins and pannexins are other adhesion mediators that form gap junctions and are involved in mechanotransduction and consecutive ATP secretion in both bone and muscle, especially as an important system in osteocytes. Connexin 43 has functions beyond the physical mechanotransduction between cells, since its knockout in early osteoblasts causes impaired muscle formation in mice [28,29].…”

Section: Mechanosensing and Mechanotransductionmentioning

confidence: 99%

Interactions between Muscle and Bone—Where Physics Meets Biology

et al. 2020

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Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment.

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Section: Mechanosensing and Mechanotransductionmentioning

confidence: 99%

Interactions between Muscle and Bone—Where Physics Meets Biology

et al. 2020

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“…ATP release and P2 receptor signaling are key modulators of skeletal development and homeostasis. Pannexin and connexin channels, P2X and P2Y receptors were detected in osteoblasts, osteoclasts, and osteocytes (Orriss et al, 2006;Plotkin et al, 2017). In osteoblasts mRNA for P2Y and P2X receptors were detected and it has been shown that their expression, as well as the amount of ATP released, depends on cellular differentiation status since osteoblasts' responsiveness to nucleotides increase in parallel with the cell differentiation and an increase of P2Y2 and P2X4 receptors was detected in mature osteoblasts compared to immature cells (Bowler et al, 1995;Maier et al, 1997;Hoebertz et al, 2000;Ihara et al, 2005;Orriss et al, 2006;Orriss et al, 2009;Orriss et al, 2012;Syberg et al, 2012).…”

Section: P2 Receptorsmentioning

confidence: 99%

Signaling of the Purinergic System in the Joint

Corciulo

Cronstein

2020

Front. Pharmacol.

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The joint is a complex anatomical structure consisting of different tissues, each with a particular feature, playing together to give mobility and stability at the body. All the joints have a similar composition including cartilage for reducing the friction of the movement and protecting the underlying bone, a synovial membrane that produces synovial fluid to lubricate the joint, ligaments to limit joint movement, and tendons for the interaction with muscles. Direct or indirect damage of one or more of the tissues forming the joint is the foundation of different pathological conditions. Many molecular mechanisms are involved in maintaining the joint homeostasis as well as in triggering disease development. The molecular pathway activated by the purinergic system is one of them.The purinergic signaling defines a group of receptors and intermembrane channels activated by adenosine, adenosine diphosphate, adenosine 5'-triphosphate, uridine triphosphate, and uridine diphosphate. It has been largely described as a modulator of many physiological and pathological conditions including rheumatic diseases. Here we will give an overview of the purinergic system in the joint describing its expression and function in the synovium, cartilage, ligament, tendon, and bone with a therapeutic perspective.

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“…Prostaglandin E2 (PGE2), a potent inflammatory cytokine produced by multiple cell types and released to the stem cell niche after muscle injury, has recently emerged as key regulator which promotes myogenic stem cell expansion and muscle regeneration, showing great potential as therapeutic target in repairing large skeletal muscle defect [47]. Among those efforts that have been made toward the elevation of PGE2, SW033291 stands out as a promising candidate.…”

Section: Discussionmentioning

confidence: 99%

Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration

Dong

Zhang

et al. 2020

Stem Cell Res Ther

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Background: The unmet medical needs in repairing large muscle defects promote the development of tissue regeneration strategy. The use of bioactive molecules in combination with biomaterial scaffold has become an area of great interest. SW033291, a small-molecule inhibitor targeting 15-hydroxyprostaglandin dehydrogenase (15-PDGH) and subsequently elevating the production of prostaglandin E2 (PGE2), has been proved to accelerate the recovery and potentiate the regeneration of multiple tissues including the bone, liver, and colon. The limited understanding of the potential therapeutic effects on myogenesis motivated us to investigate the role of SW033291 in regulating muscle-derived stem cell (MDSC) myogenic differentiation and MDSC-mediated muscle regeneration. Methods: The characteristics of rat MDSCs, including cell-specific markers and myogenic differentiation potential, were determined. MDSCs were incubated with SW033291 to evaluate PGE2 production and cytotoxicity. The effects of SW033291 on MDSC myogenic differentiation were assessed by quantitative real-time polymerase chain reaction (qPCR), western blot, and immunocytochemistry. The fibrin gel containing MDSCs and SW033291 was used for muscle regeneration in a tibialis anterior muscle defect model. Results: Our data demonstrated that MDSCs were well-tolerated to SW033291 and treatment with SW033291 significantly promoted the production of PGE2 by MDSCs. In vitro analysis showed that SW033291 enhanced the myogenic differentiation and myotube formation by upregulating a series of myogenic markers. Additionally, the activation of PI3K/Akt pathway was involved in the mechanism underlying these promotive effects. Then, in situ casting of fibrin gel containing MDSCs and SW033291 was used to repair the tibialis anterior muscle defect; the addition of SW033291 significantly promoted myofiber formation within the defect region with mild immune response, less fibrosis, and sufficient vascularization. Conclusion: SW033291 acted as a positive regulator of MDSC myogenic differentiation, and incorporating the compound with MDSCs in fibrin gel could serve as an effective method to repair large skeletal muscle defects.

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Connexins and Pannexins in Bone and Skeletal Muscle

Cited by 44 publications

References 104 publications

Interactions between Muscle and Bone—Where Physics Meets Biology

Interactions between Muscle and Bone—Where Physics Meets Biology

Signaling of the Purinergic System in the Joint

Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration

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