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Current Osteoporosis Reports Oct 2019Bone and muscle mass increase in response to mechanical loading and biochemical cues. Bone-forming osteoblasts differentiate into early osteocytes which ultimately... (Review)
Review
PURPOSE OF REVIEW
Bone and muscle mass increase in response to mechanical loading and biochemical cues. Bone-forming osteoblasts differentiate into early osteocytes which ultimately mature into late osteocytes encapsulated in stiff calcified matrix. Increased muscle mass originates from muscle stem cells (MuSCs) enclosed between their plasma membrane and basal lamina. Stem cell fate and function are strongly determined by physical and chemical properties of their microenvironment, i.e., the cell niche.
RECENT FINDINGS
The cellular niche is a three-dimensional structure consisting of extracellular matrix components, signaling molecules, and/or other cells. Via mechanical interaction with their niche, osteocytes and MuSCs are subjected to mechanical loads causing deformations of membrane, cytoskeleton, and/or nucleus, which elicit biochemical responses and secretion of signaling molecules into the niche. The latter may modulate metabolism, morphology, and mechanosensitivity of the secreting cells, or signal to neighboring cells and cells at a distance. Little is known about how mechanical loading of bone and muscle tissue affects osteocytes and MuSCs within their niches. This review provides an overview of physicochemical niche conditions of (early) osteocytes and MuSCs and how these are sensed and determine cell fate and function. Moreover, we discuss how state-of-the-art imaging techniques may enhance our understanding of these conditions and mechanisms.
Topics: Animals; Cell Differentiation; Extracellular Matrix; Humans; Mechanotransduction, Cellular; Muscle Cells; Osteocytes; Stress, Mechanical
PubMed: 31428977
DOI: 10.1007/s11914-019-00522-0 -
Respiratory Research Apr 2017Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a... (Review)
Review
Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a polarized cellular process involving a protrusive cell front and a retracting trailing rear. There are three cytoskeletal systems in mammalian cells: the actin cytoskeleton, the intermediate filament network, and microtubules; all of which regulate all or part of the migrated process. The dynamic actin cytoskeleton spatially and temporally regulates protrusion, adhesions, contraction, and retraction from the cell front to the rear. c-Abl tyrosine kinase plays a critical role in regulating actin dynamics and migration of airway smooth muscle cells and nonmuscle cells. Recent studies suggest that intermediate filaments undergo reorganization during migration, which coordinates focal adhesion dynamics, cell contraction, and nucleus rigidity. In particular, vimentin intermediate filaments undergo phosphorylation and reorientation in smooth muscle cells, which may regulate cell contraction and focal adhesion assembly/disassembly. Motile cells are characterized by a front-rear polarization of the microtubule framework, which regulates all essential processes leading to cell migration through its role in cell mechanics, intracellular trafficking, and signaling. This review recapitulates our current knowledge how the three cytoskeletal systems spatially and temporally modulate the migratory properties of cells. We also summarize the potential role of migration-associated biomolecules in lung and vascular diseases.
Topics: Actin Cytoskeleton; Animals; Cell Movement; Cells, Cultured; Cytoskeleton; Humans; Microtubules; Models, Biological; Myocytes, Smooth Muscle
PubMed: 28390425
DOI: 10.1186/s12931-017-0544-7 -
Vascular Pharmacology Oct 2023Vascular endothelial and smooth muscle cell dysfunction proceed the development of numerous vascular diseases, such as atherosclerosis. Both estrogen and progesterone... (Review)
Review
Vascular endothelial and smooth muscle cell dysfunction proceed the development of numerous vascular diseases, such as atherosclerosis. Both estrogen and progesterone receptors are present on vascular endothelial and smooth muscle cells, and therefore it has been postulated that these compounds may affect vascular function. It has been well-established that estrogen is a vasoprotective compound, however, the effects of progesterone on vascular function are not well understood. This narrative review summarizes the current research investigating the impact of both endogenous progesterone, and exogenous synthetic progestin on vascular endothelial and smooth muscle cell function and identifies discrepancies on their effects in vitro and in vivo. We speculate that an inverted-U dose response curve may exist between nitric oxide bioavailability and progesterone concentration, and that the androgenic properties of a progestin may influence vascular function. Future research is needed to discern the effects of both endogenous progesterone and exogenous progestin on vascular endothelial and smooth muscle cell function with consideration for the impacts of progesterone/progestin dose, and progestin type.
Topics: Humans; Progestins; Progesterone; Progesterone Congeners; Estrogens; Endothelial Cells; Atherosclerosis; Myocytes, Smooth Muscle
PubMed: 37591444
DOI: 10.1016/j.vph.2023.107209 -
Physiological Reviews Oct 2021The design of the energy metabolism system in striated muscle remains a major area of investigation. Here, we review our current understanding and emerging hypotheses... (Review)
Review
The design of the energy metabolism system in striated muscle remains a major area of investigation. Here, we review our current understanding and emerging hypotheses regarding the metabolic support of muscle contraction. Maintenance of ATP free energy, so called energy homeostasis, via mitochondrial oxidative phosphorylation is critical to sustained contractile activity, and this major design criterion is the focus of this review. Cell volume invested in mitochondria reduces the space available for generating contractile force, and this spatial balance between mitochondria acontractile elements to meet the varying sustained power demands across muscle types is another important design criterion. This is accomplished with remarkably similar mass-specific mitochondrial protein composition across muscle types, implying that it is the organization of mitochondria within the muscle cell that is critical to supporting sustained muscle function. Beyond the production of ATP, ubiquitous distribution of ATPases throughout the muscle requires rapid distribution of potential energy across these large cells. Distribution of potential energy has long been thought to occur primarily through facilitated metabolite diffusion, but recent analysis has questioned the importance of this process under normal physiological conditions. Recent structural and functional studies have supported the hypothesis that the mitochondrial reticulum provides a rapid energy distribution system via the conduction of the mitochondrial membrane potential to maintain metabolic homeostasis during contractile activity. We extensively review this aspect of the energy metabolism design contrasting it with metabolite diffusion models and how mitochondrial structure can play a role in the delivery of energy in the striated muscle.
Topics: Animals; Energy Metabolism; Humans; Mitochondria, Muscle; Muscle Cells; Muscle, Striated
PubMed: 33733879
DOI: 10.1152/physrev.00040.2020 -
Cellular Signalling Jan 2019Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a... (Review)
Review
Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a pathophysiological response to acute or chronic sources of vascular damage that can lead to occlusive narrowing of the vessel lumen. Atherosclerosis, the primary cause of coronary artery disease, is characterised by chronic vascular inflammation and dyslipidemia, while revascularisation surgeries such as coronary stenting and bypass grafting represent acute forms of vascular injury. Gene knockouts of transforming growth factor-beta (TGFβ), its receptors and downstream signalling proteins have demonstrated the importance of this pleiotropic cytokine during vasculogenesis and in the maintenance of vascular homeostasis. Dysregulated TGFβ signalling is a hallmark of many vascular diseases, and has been associated with the induction of pathological vascular cell phenotypes, fibrosis and ECM remodelling. Here we present an overview of TGFβ signalling in SMCs, highlighting the ways in which this multifaceted cytokine regulates SMC behaviour and phenotype in cardiovascular diseases driven by intimal hyperplasia.
Topics: Animals; Cell Movement; Cell Proliferation; Coronary Artery Disease; Humans; Myocytes, Smooth Muscle; Signal Transduction; Transforming Growth Factor beta
PubMed: 30227237
DOI: 10.1016/j.cellsig.2018.09.004 -
International Journal of Molecular... Sep 2021Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in... (Review)
Review
Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in peripheral arterial disease patients. Vascular smooth muscle cells (VSMCs) are the predominant cell type in collateral arteries and respond to altered blood flow and inflammatory conditions after an arterial occlusion by switching their phenotype between quiescent contractile and proliferative synthetic states. Maintaining the contractile state of VSMC is required for collateral vascular function to regulate blood vessel tone and blood flow during arteriogenesis, whereas synthetic SMCs are crucial in the growth and remodeling of the collateral media layer to establish more stable conduit arteries. Timely VSMC phenotype switching requires a set of coordinated actions of molecular and cellular mediators to result in an expansive remodeling of collaterals that restores the blood flow effectively into downstream ischemic tissues. This review overviews the role of VSMC phenotypic switching in the physiological arteriogenesis process and how the VSMC phenotype is affected by the primary triggers of arteriogenesis such as blood flow hemodynamic forces and inflammation. Better understanding the role of VSMC phenotype switching during arteriogenesis can identify novel therapeutic strategies to enhance revascularization in peripheral arterial disease.
Topics: Animals; Arterial Occlusive Diseases; Arteries; Cell Proliferation; Collateral Circulation; Gene Expression; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenotype; Vascular Remodeling
PubMed: 34638923
DOI: 10.3390/ijms221910585 -
Molecular Aspects of Medicine Apr 2018Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a... (Review)
Review
Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a better understanding of the surface markers that characterize exosomes and microvesicles, and greater information derived from -omics approaches on the proteins, lipids, mRNAs, and microRNAs (miRNAs) transported by EVs. We have recently discovered a role for exosome-derived miRNAs in age-related bone loss and osteoarthritis, two conditions that impose a significant public health burden on the aging global population. Previous work has also revealed multiple roles for EVs and their miRNAs in muscle regeneration and congenital myopathies. Thus, EVs appear to be involved in a number of degenerative conditions that impact the musculoskeletal system, indicating that the musculoskeletal system is an excellent model for investigating the role of EVs in tissue maintenance and repair. This review highlights the role of EVs in bone, skeletal muscle, and joint health, including both normal tissue metabolism as well as tissue injury repair and regeneration. A consistent theme that emerges from study of musculoskeletal EVs is that various miRNAs appear to mediate a number of key pathological processes. These findings point to a potential therapeutic opportunity to target EV-derived miRNAs as a strategy for improving musculoskeletal function.
Topics: Animals; Biomarkers; Bone and Bones; Cell Differentiation; Disease Susceptibility; Extracellular Vesicles; Humans; Joint Diseases; Muscle Cells; Musculoskeletal Diseases; Osteoporosis; Regeneration
PubMed: 28965750
DOI: 10.1016/j.mam.2017.09.006 -
International Journal of Molecular... Oct 2020Many studies evaluated the short-term in vitro toxicity of nanoparticles (NPs); however, long-term effects are still not adequately understood. Here, we investigated the...
Many studies evaluated the short-term in vitro toxicity of nanoparticles (NPs); however, long-term effects are still not adequately understood. Here, we investigated the potential toxic effects of biomedical (polyacrylic acid and polyethylenimine coated magnetic NPs) and two industrial (SiO and TiO) NPs following different short-term and long-term exposure protocols on two physiologically different in vitro models that are able to differentiate: L6 rat skeletal muscle cell line and biomimetic normal porcine urothelial (NPU) cells. We show that L6 cells are more sensitive to NP exposure then NPU cells. Transmission electron microscopy revealed an uptake of NPs into L6 cells but not NPU cells. In L6 cells, we obtained a dose-dependent reduction in cell viability and increased reactive oxygen species (ROS) formation after 24 h. Following continuous exposure, more stable TiO and polyacrylic acid (PAA) NPs increased levels of nuclear factor Nrf2 mRNA, suggesting an oxidative damage-associated response. Furthermore, internalized magnetic PAA and TiO NPs hindered the differentiation of L6 cells. We propose the use of L6 skeletal muscle cells and NPU cells as a novel approach for assessment of the potential long-term toxicity of relevant NPs that are found in the blood and/or can be secreted into the urine.
Topics: Animals; Cell Line; Cell Survival; Cells, Cultured; Epithelial Cells; Muscle Cells; NF-E2-Related Factor 2; Nanoparticles; Polyesters; Rats; Reactive Oxygen Species; Swine; Titanium; Toxicity Tests; Urothelium
PubMed: 33066271
DOI: 10.3390/ijms21207545 -
Cells Apr 2022Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover... (Review)
Review
Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.
Topics: Coculture Techniques; Drug Development; Humans; Muscle Cells; Neuromuscular Diseases; Organoids
PubMed: 35406795
DOI: 10.3390/cells11071233 -
Cells Mar 2022(1) Abdominal aortic aneurysm (AAA) is a silent, progressive disease with significant mortality from rupture. Whilst screening programmes are now able to detect this...
(1) Abdominal aortic aneurysm (AAA) is a silent, progressive disease with significant mortality from rupture. Whilst screening programmes are now able to detect this pathology early in its development, no therapeutic intervention has yet been identified to halt or retard aortic expansion. The inability to obtain aortic tissue from humans at early stages has created a necessity for laboratory models, yet it is essential to create a timeline of events from EARLY to END stage AAA progression. (2) We used a previously validated ex vivo porcine bioreactor model pre-treated with protease enzyme to create "aneurysm" tissue. Mechanical properties, histological changes in the intact vessel wall, and phenotype/function of vascular smooth muscle cells (SMC) cultured from the same vessels were investigated. (3) The principal finding was significant hyperproliferation of SMC from EARLY stage vessels, but without obvious histological or SMC aberrancies. END stage tissue exhibited histological loss of α-smooth muscle actin and elastin; mechanical impairment; and, in SMC, multiple indications of senescence. (4) Aortic SMC may offer a therapeutic target for intervention, although detailed studies incorporating intervening time points between EARLY and END stage are required. Such investigations may reveal mechanisms of SMC dysfunction in AAA development and hence a therapeutic window during which SMC differentiation could be preserved or reinstated.
Topics: Animals; Aortic Aneurysm, Abdominal; Cell Differentiation; Myocytes, Smooth Muscle; Phenotype; Swine
PubMed: 35326494
DOI: 10.3390/cells11061043