scholarly journals Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Lei Qin ◽  
Tailin He ◽  
Sheng Chen ◽  
Dazhi Yang ◽  
Weihong Yi ◽  
...  

AbstractMechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal environments. The mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in cells. The Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus far. The regulation of two family members, Piezo1 and Piezo2, has been reported to have essential functions in mechanosensation and transduction in different organs and tissues. Recently, the predominant contributions of the Piezo family were reported to occur in the skeletal system, especially in bone development and mechano-stimulated bone homeostasis. Here we review current studies focused on the tissue-specific functions of Piezo1 and Piezo2 in various backgrounds with special highlights on their importance in regulating skeletal cell mechanotransduction. In this review, we emphasize the diverse functions of Piezo1 and Piezo2 and related signaling pathways in osteoblast lineage cells and chondrocytes. We also summarize our current understanding of Piezo channel structures and the key findings about PIEZO gene mutations in human diseases.

2018 ◽  
Vol 98 (3) ◽  
pp. 1083-1112 ◽  
Author(s):  
Florent Elefteriou

It is from the discovery of leptin and the central nervous system as a regulator of bone remodeling that the presence of autonomic nerves within the skeleton transitioned from a mere histological observation to the mechanism whereby neurons of the central nervous system communicate with cells of the bone microenvironment and regulate bone homeostasis. This shift in paradigm sparked new preclinical and clinical investigations aimed at defining the contribution of sympathetic, parasympathetic, and sensory nerves to the process of bone development, bone mass accrual, bone remodeling, and cancer metastasis. The aim of this article is to review the data that led to the current understanding of the interactions between the autonomic and skeletal systems and to present a critical appraisal of the literature, bringing forth a schema that can put into physiological and clinical context the main genetic and pharmacological observations pointing to the existence of an autonomic control of skeletal homeostasis. The different types of nerves found in the skeleton, their functional interactions with bone cells, their impact on bone development, bone mass accrual and remodeling, and the possible clinical or pathophysiological relevance of these findings are discussed.


2009 ◽  
Vol 15 (3_suppl) ◽  
pp. 1-12 ◽  
Author(s):  
O Garcea ◽  
A Villa1 ◽  
F Cáceres ◽  
T Adoni ◽  
M Alegría ◽  
...  

Patients with clinically isolated syndrome (CIS) by definition do not have multiple sclerosis (MS) but are at risk of developing it. While studies show earlier immunomodulating drug use is effective, treatment must consider likely patient prognosis. In this paper we review current diagnosis, prognosis, and treatment literature for patients with CIS within Latin American clinical settings. Latin American MS experts, convened by ACINDES (The Civil Association for Research and Development in Health), reviewed current CIS (and early MS) literature and drew consensus conclusions. Three subgroups addressed separate questionnaires on CIS issues: prognosis, diagnosis, and treatment. MRI can contribute to predicting MS risk in patients with CIS; in Latin America, investigation of haplotype presence associated with CIS would be appropriate. McDonald's criteria and subsequent revisions enable earlier, more accurate MS diagnosis. Type A evidence exists supporting all leading immunomodulating MS drugs for effective treatment of CIS with a high risk of conversion to MS. In conclusion, patients with CIS are usually young, with often-limited symptomatic manifestations, and must be adequately prepared to receive preventive treatment. This consensus review should contribute to the dialogue between physicians and patients. Multiple Sclerosis 2009; 15: S1–S12. http://msj.sagepub.com


Many leading nineteenth-century physicians recognized the need to reduce the empirical element in medicine and to base both diagnosis and treatment more firmly upon scientific principles. In an age when chemistry was a rapidly developing science it seemed that animal chemistry, dealing with the materials and functions of living organisms, might well offer the best solution to the problem. Thus the development of the subject for medical purposes became one of the main objectives of animal chemists, although from hindsight it is clear that neither the techniques nor the chemical knowledge available were at all adequate for solving the complex problems involved. Yet chemists like Fourcroy and Berzelius tried to understand the chemistry of life and their results seemed to support the widely held view that a knowledge of the composition of animal tissues, together with an understanding of the natural functions in health, would aid medical diagnosis and treatment by exposing the faults present in disease. In early nineteenth-century England there was a lively interest in this subject (I) and some physicians became very successful in applying chemical principles to medicine, but despite the evident value of animal chemistry the novelty of the subject caused medical schools to be reluctant to introduce it into their curricula. Medical students continued to receive instruction in the classics but the physical sciences were frequently neglected.


Blood ◽  
2021 ◽  
Author(s):  
Katya Ravid ◽  
Aikaterini Karagianni

Myeloproliferative Neoplasms (MPNs) are a heterogeneous group of chronic hematological diseases that arise from the clonal expansion of abnormal hematopoietic stem cells, of which Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF) have been extensively reviewed in context of clonal expansion, fibrosis and other phenotypes. Here, we review current knowledge on the influence of different forms of MPN on bone health. Studies implicated various degrees of effect of different forms of MPN on bone density, and on osteoblast proliferation and differentiation, using murine models and human data. The majority of studies show that bone volume is generally increased in PMF patients, whereas it is slightly decreased or not altered in ET and PV patients, although possible differences between male and female phenotypes were not fully explored in most MPN forms. Osteosclerosis seen in PMF patients is a serious complication that can lead to bone marrow failure, and the loss of bone reported in some ET and PV patients can lead to osteoporotic fractures. Some MPN forms are associated with increased number of megakaryocytes (MKs), and several of the MK-associated factors in MPN are known to affect bone development. Here, we review known mechanisms involved in these processes, with focus on the role of MKs and secreted factors. Understanding MPN-associated changes in bone health could improve early intervention and treatment of this side effect of the pathology.


2020 ◽  
Vol 21 (24) ◽  
pp. 9426
Author(s):  
Enrica Urciuoli ◽  
Barbara Peruzzi

Mechanotransduction is a physiological process in which external mechanical stimulations are perceived, interpreted, and translated by cells into biochemical signals. Mechanical stimulations exerted by extracellular matrix stiffness and cell–cell contacts are continuously applied to living cells, thus representing a key pivotal trigger for cell homeostasis, survival, and function, as well as an essential factor for proper organ development and metabolism. Indeed, a deregulation of the mechanotransduction process consequent to gene mutations or altered functions of proteins involved in perceiving cellular and extracellular mechanics can lead to a broad range of diseases, from muscular dystrophies and cardiomyopathies to cancer development and metastatization. Here, we recapitulate the involvement of focal adhesion kinase (FAK) in the cellular conditions deriving from altered mechanotransduction processes.


2016 ◽  
Vol 60 (3) ◽  
pp. 349-355 ◽  
Author(s):  
Ewa Tomaszewska ◽  
Siemowit Muszyński ◽  
Piotr Dobrowolski ◽  
Krzysztof Kostro ◽  
Iwona Taszkun ◽  
...  

AbstractIntroduction: The aim of this study was to determine the effect of deoxynivalenol (DON), given alone or with bentonite (which eliminates mycotoxicity) in the diet of mink dams throughout mating, pregnancy, and lactation period to pelt harvesting, on the mechanical properties and geometry of their long bones.Material and Methods: The minks were randomly assigned into two groups: a control group (not supplemented with DON, n = 15) and a group fed naturally DON-contaminated wheat and divided into three sub-groups (each sub-group n = 15), depending on bentonite dose: 0 M – sub-group fed naturally DON-contaminated wheat at a concentration of 3.7 mg kg−1 alone; 2 M – sub-group fed naturally DON-contaminated wheat at a concentration of 3.7 mg kg−1 and bentonite at a concentration of 2 kg 1000 kg−1; 0.5 M – sub-group fed naturally DON-contaminated wheat at a concentration of 3.7 mg kg−1 and bentonite at a concentration of 0.5 kg 1000 kg−1.Results: The DON treatment reduced the length of the femur compared to the control group and reduced the bone weight dependently on the amount of bentonite supplementation. However, DON treatment reduced the MRWT and CI of the femur, irrespective of the bentonite supplementation, compared to the control. The total BTD and BMC decreased in all DON-treated groups (irrespective of the bentonite supplementation). Furthermore, the densitometric analysis showed that the main changes in BMD and BMC indicated bone loss in the proximal and distal parts of bone covering the trabecular bone; whereas when bentonite was given at the dose of 2 kg 1000 kg−1 an increase in the whole BMD and BMC was observed in the femoral midshaft.Conclusion: Analysis of the geometrical parameters seems to indicate that endosteal resorption was delayed after bentonite supplementation. The addition of bentonite diminished the DON action on bone homeostasis in the mink dams. Thus bentonite could prevent DON-induced bone loss in a dose-dependent manner.


Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 138
Author(s):  
Núria Martínez-Gil ◽  
Nerea Ugartondo ◽  
Daniel Grinberg ◽  
Susanna Balcells

The Wnt pathway is involved in several processes essential for bone development and homeostasis. For proper functioning, the Wnt pathway is tightly regulated by numerous extracellular elements that act by both activating and inhibiting the pathway at different moments. This review aims to describe, summarize and update the findings regarding the extracellular modulators of the Wnt pathway, including co-receptors, ligands and inhibitors, in relation to bone homeostasis, with an emphasis on the animal models generated, the diseases associated with each gene and the bone processes in which each member is involved. The precise knowledge of all these elements will help us to identify possible targets that can be used as a therapeutic target for the treatment of bone diseases such as osteoporosis.


Author(s):  
Fangyuan Shen ◽  
Yu Shi

Osteoblasts continuously replenished by osteoblast progenitor cells form the basis of bone development, maintenance, and regeneration. Mesenchymal stem cells (MSCs) from various tissues can differentiate into the progenitor cell of osteogenic lineage and serve as the main source of osteoblasts. They also respond flexibly to regenerative and anabolic signals emitted by the surrounding microenvironment, thereby maintaining bone homeostasis and participating in bone remodeling. However, MSCs exhibit heterogeneity at multiple levels including different tissue sources and subpopulations which exhibit diversified gene expression and differentiation capacity, and surface markers used to predict cell differentiation potential remain to be further elucidated. The rapid advancement of lineage tracing methods and single-cell technology has made substantial progress in the characterization of osteogenic stem/progenitor cell populations in MSCs. Here, we reviewed the research progress of scRNA-seq technology in the identification of osteogenic markers and differentiation pathways, MSC-related new insights drawn from single-cell technology combined with experimental technology, and recent findings regarding the interaction between stem cell fate and niche in homeostasis and pathological process.


Author(s):  
Iris Verbinnen ◽  
Pieter Vaneynde ◽  
Sara Reynhout ◽  
Lisa Lenaerts ◽  
Rita Derua ◽  
...  

By removing Ser/Thr-specific phosphorylations in a multitude of protein substrates in diverse tissues, Protein Phosphatase type 2A (PP2A) enzymes play essential regulatory roles in cellular signalling and physiology, including in brain function and development. Here, we review current knowledge on PP2A gene mutations causally involved in neurodevelopmental disorders and intellectual disability, focusing on PPP2CA, PPP2R1A and PPP2R5D. We provide insights into the impact of these mutations on PP2A structure, substrate specificity and potential function in neurobiology and brain development.


2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Louisa Johanna Du Toit

Dark Green Religion (DGR), is an umbrella term formulated by Bron Taylor, to describe nature revering movements that do not fit into the category of organized religion. These movements use religious-like emotions to express their convictions and display a sincere commitment towards the environment. A central focus of DGR is a deep-felt kinship with all living organisms on Earth (arising from a Darwinian understanding that all forms of life have developed from a common ancestor), accompanied by feelings of humility coupled with a critical view of human moral superiority. This article presents a Dark Green Religious analysis of the life and work of Wangari Maathai (1940-2011). She was the first woman in East Africa to receive a doctorate, and was awarded the Nobel Peace Prize in 2004 for her work with the Green Belt Movement (GBM). In the DGR analysis, it is illustrated that the principles of belonging, interconnectedness and sacredness are revealed through Maathai’s written legacy. Evidence is also presented that she could be viewed as an example of Naturalistic Gaianism, one of the four types of DGR. In conclusion, a link between ecofeminism and DGR is proposed by highlighting the shared concepts between the two phenomena.


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