The cilium as a force sensor−myth versus reality

Ferreira, Rita R.; Fukui, Hajime; Chow, Renée; Vilfan, Andrej; Vermot, Julien

doi:10.1242/jcs.213496

Cited by 78 publications

(67 citation statements)

References 135 publications

(158 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With slight variability concerning differential channel expression, virtually all bone cells express the necessary tools, including the primary cilium. The evidence for the relevance of fluid flow and deflection of primary cilia comes from in vitro studies but also from knockout (KO) mouse experiments that impair primary cilia development, but there is still some debate about the contributions and their molecular mechanisms related to primary cilia in mechanotransduction elicited by fluid flow [9,[36][37][38][39]. Within the huge network of cellular dendritic processes of osteocytes, there is regular fluid flow, which also supports nutrient and waste transport.…”

Section: Mechanosensing and Mechanotransductionmentioning

confidence: 99%

Interactions between Muscle and Bone—Where Physics Meets Biology

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Mechanosensing and Mechanotransductionmentioning

confidence: 99%

Interactions between Muscle and Bone—Where Physics Meets Biology

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Among a variety of mechanotransduction mechanisms involved in MSC differentiation, primary cilium is one of the most peculiar. 59,60 The primary (nonmotile) cilium is present on the surface of different types of mammalian cells. 61 Sensing is performed by cilium bending that occurs in response to shear stress 62 or mechanical tension produced by compression forces.…”

Section: Primary Ciliummentioning

confidence: 99%

Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

Saidova

Vorobjev

2020

Tissue Engineering Part B: Reviews

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) from adult tissues are promising candidates for personalized cell therapy and tissue engineering. Significant progress was achieved in our understanding of the regulation of MSCs proliferation and differentiation by different cues during the past years. Proliferation and differentiation of MSCs are sensitive to the extracellular matrix (ECM) properties, physical cues, and chemical signaling. Sheath stress, matrix stiffness, surface adhesiveness, and micro-and nanotopography define cell shape and dictate lineage commitment of MSCs even in the absence of specific chemical signals. We discuss mechanotransduction as the major route from ECM through the cytoskeleton toward signaling pathways and gene expression. All components of the cytoskeleton from primary cilium and focal adhesions (FAs) to actin, microtubules (MTs), and intermediate filaments (IFs) are involved in the mechanotransduction. Differentiation of MSCs is regulated via the complex network of interrelated signaling pathways, including RhoA/ROCK, Akt/Erk, and YAP/TAZ effectors of Hippo pathway. These pathways could be regulated both by chemical and mechanical stimuli. Attenuation of these pathways in MSCs results in specific changes in FAs and actin cytoskeleton. Besides, differentiation of MSCs affects MTs and IFs. Recent findings highlight the role of intranuclear actin in the regulation of transcription factors in response to mechanical environmental stimuli. Alterations of cytoskeletal components reflect the MSC senescence state and their migratory capacity. In this review, we discuss the relationships between the molecular interactions in signaling pathways and morphological response of cytoskeletal components and reveal the complex interrelations between cytoskeleton systems and signaling pathways during lineage commitment of MSCs.

show abstract

“…Upon exposure to an external force, the cilia bend, activating downstream signaling pathways (Fig. 1b) [48,51]. While it is widely accepted that primary cilia are mechanosensitive, the mechanisms regulating this ability are still under debate [51].…”

Section: Primary Ciliamentioning

confidence: 99%

Mechanoregulation in Hematopoiesis and Hematologic Disorders

2020

View full text Add to dashboard Cite

Purpose of Review Hematopoietic stem cells (HSCs) are reliant on intrinsic and extrinsic factors for tight control of self-renewal, quiescence, differentiation, and homing. Given the intimate relationship between HSCs and their niche, increasing numbers of studies are examining how biophysical cues in the hematopoietic microenvironment impact HSC functions. Recent Findings Numerous mechanosensors are present on hematopoietic cells, including integrins, mechanosensitive ion channels, and primary cilia. Integrin-ligand adhesion, in particular, has been found to be critical for homing and anchoring of HSCs and progenitors in the bone marrow. Integrin-mediated interactions with ligands present on extracellular matrix and endothelial cells are key to establishing long-term engraftment and quiescence of HSCs. Importantly, disruption in the architecture and cellular composition of the bone marrow associated with conditioning regimens and primary myelofibrosis exposes HSCs to a profoundly distinct mechanical environment, with potential implications for progression of hematologic dysfunction and pathologies. Summary Study of the mechanobiological signals that govern hematopoiesis represents an important future step toward understanding HSC biology in homeostasis, aging, and cancer.

show abstract

The cilium as a force sensor−myth versus reality

Cited by 78 publications

References 135 publications

Interactions between Muscle and Bone—Where Physics Meets Biology

Interactions between Muscle and Bone—Where Physics Meets Biology

Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

Mechanoregulation in Hematopoiesis and Hematologic Disorders

Contact Info

Product

Resources

About