Delayed Onset Muscle Soreness and Critical Neural Microdamage-Derived Neuroinflammation

Biomolecules, Journal Year: 2022, Volume and Issue: 12(9), P. 1207 - 1207

Published: Aug. 31, 2022

Piezo2 transmembrane excitatory mechanosensitive ion channels were identified as the principal mechanotransduction for proprioception. Recently, it was postulated that could be acutely microdamaged on an autologous basis at proprioceptive Type Ia terminals in a cognitive demand-induced acute stress response time window when unaccustomed or strenuous eccentric contractions are executed. One consequence of this proposed transient microinjury VGLUT1/Ia synaptic disconnection motoneurons, we can learn from platinum-analogue chemotherapy. A secondary, harsher injury phase with involvement polymodal Aδ and nociceptive C-fibers follow primary impairment proprioception delayed onset muscle soreness. Repetitive reinjury these form repeated bout effects is to tertiary phase. Notably, use associated motor learning memory. The monosynaptic static firing sensory encoding affected stretch reflex immediate microdamage leading impaired proprioception, exaggerated reduced range motion. These channelopathies afferent constitute critical gateway pathophysiology Correspondingly, fatiguing contraction-based pathological hyperexcitation afferents induces reactive oxygen species production-associated neuroinflammation neuronal activation spinal cord

Language: Английский

---

Miswired Proprioception in Amyotrophic Lateral Sclerosis in Relation to Pain Sensation (and in Delayed Onset Muscle Soreness)—Is Piezo2 Channelopathy a Principal Transcription Activator in Proprioceptive Terminals Besides Being the Potential Primary Damage?

Life, Journal Year: 2023, Volume and Issue: 13(3), P. 657 - 657

Published: Feb. 27, 2023

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative multisystem disease, with an unknown pathomechanism, resulting in progressive motoneuron loss. In 90-95% of cases, ALS sporadic, but close to 10% familial inherited gene mutations from family members. Recently, non-contact dying-back injury mechanism theory postulated that irreversible intrafusal proprioceptive terminal degeneration induces the non-resolving impairment circuitry, leading loss, overloading and depletion central nervous system, eventually death. The current manuscript proposes Piezo2 channelopathy this constantly activated dysregulated transcription process ALS, providing access underlying pathogenic variants letting cell-type-specific noncoding DNA become more apparent. This opinion piece genes are associated both downstream upstream, their mutations, along aging process, could explain ALS. Moreover, microinjury ion channel be primary damage or root cause death Finally, also depicts pathomechanism as why considered painless disease.

Language: Английский

---

The emerging role of Piezo1 in the musculoskeletal system and disease

Theranostics, Journal Year: 2024, Volume and Issue: 14(10), P. 3963 - 3983

Published: Jan. 1, 2024

Piezo1, a mechanosensitive ion channel, has emerged as key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such lymphatic vessel development, axon growth, vascular immunoregulation, blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, homeostasis, recently attracted attention regarding the significance of Piezo1. This review aims to provide comprehensive summary current research on Piezo1 highlighting its impact bone formation, myogenesis, chondrogenesis, intervertebral disc tendon matrix cross-linking, physical activity. Additionally, we explore potential targeting therapeutic approach disorders, including osteoporosis, muscle atrophy, degeneration, osteoarthritis.

Language: Английский

---

Regulation and mechanistic insights into tensile strain in mesenchymal stem cell osteogenic differentiation

Bone, Journal Year: 2024, Volume and Issue: 187, P. 117197 - 117197

Published: Oct. 1, 2024

Language: Английский

---

Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy

Journal of Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 72(8), P. 1598 - 1608

Published: May 4, 2022

Dry eye disease (DED) is a multifactorial disorder with recognized pathology, but not entirely known pathomechanism. It suggested to represent continuum neuropathic corneal pain the paradox that DED pain-free in most cases, although it regarded as condition. The current paper puts into perspective one gateway from physiology pathophysiology could be Piezo2 channelopathy, opening pathway potentially quad-phasic non-contact injury mechanism on basis and heterogeneous clinical picture. primary phase microinjury of ion channel at somatosensory nerve terminal. secondary involves harsher tissue damage C-fiber contribution due lost or inadequate intimate cross-talk between peripheral Piezo1. third this neuronal sensitization process underlying repeated re-injury Piezo2, leading proposed chronic channelopathy. Notably, may evolve certain cases absence second phase. Finally, quadric lingering low-grade neuroinflammation associated aging, called inflammaging. This clinically initiate augment DED, explaining why increasing age risk factor. We highlight potential role NGF-TrkA axis signaling further promote stress-derived hyperexcited state. NGF-TrkA-Piezo2 might explain female sex represents factor for DED.

Language: Английский

---

Aberrant mechanical loading induces annulus fibrosus cells apoptosis in intervertebral disc degeneration via mechanosensitive ion channel Piezo1

Arthritis Research & Therapy, Journal Year: 2023, Volume and Issue: 25(1)

Published: July 7, 2023

Intervertebral disc degeneration (IVDD) is closely associated with the structural damage in annulus fibrosus (AF). Aberrant mechanical loading an important inducement of cells (AFCs) apoptosis, which contributes to AF and aggravates IVDD, but underlying mechanism still unclear. This study aims investigate a mechanosensitive ion channel protein Piezo1 aberrant loading-induced AFCs apoptosis IVDD.Rats were subjected lumbar instability surgery induce unbalanced dynamic static forces establish model. MRI histological staining used evaluate IVDD degree. A cyclic stretch (CMS)-stimulated model was established by Flexcell system vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, flow cytometry level. The activation detected using western blot calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, lentiviral shRNA-Piezo1 (Lv-Piezo1) utilized regulate function Piezo1. High-throughput RNA sequencing (RNA-seq) explore Piezo1-induced apoptosis. Calpain activity Calpain2/Bax/Caspase3 axis evaluated kit siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration Lv-Piezo1 therapeutic effect silencing rats.Lumbar promoted expression stimulated rats 4 weeks after surgery. CMS elicited distinct AFCs, enhanced activation. Yoda1 further CMS-induced while GSMTx4 exhibited opposite effects. RNA-seq showed that knocking down inhibited signaling pathway. elevated BAX cleaved-Caspase3. Calpain2, not Calpain1 knockdown, cleaved-Caspase3 alleviated significantly progress surgery.Aberrant induces promote activating downstream Calpain2/BAX/Caspase3 expected be target treating IVDD.

Language: Английский

---

Towards Polycaprolactone-Based Scaffolds for Alveolar Bone Tissue Engineering: A Biomimetic Approach in a 3D Printing Technique

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16180 - 16180

Published: Nov. 10, 2023

The alveolar bone is a unique type of bone, and the goal tissue engineering (BTE) to develop methods facilitate its regeneration. Currently, an emerging trend involves fabrication polycaprolactone (PCL)-based scaffolds using three-dimensional (3D) printing technique enhance osteoconductive architecture. These are further modified with hydroxyapatite (HA), I collagen (CGI), or chitosan (CS) impart high osteoinductive potential. In conjunction cell therapy, these may serve as appealing alternative autografts. This review discusses research gaps in designing 3D-printed PCL-based from biomimetic perspective. article begins systematic analysis biological mineralisation (biomineralisation) ossification optimise scaffold's structural, mechanical, degradation, surface properties. scaffold-designing strategy lays groundwork for developing pathway that spans fundamental principles such molecular dynamics (MD) simulations techniques. Ultimately, this paves way vitro vivo studies, leading potential clinical applications.

Language: Английский

---

Biomaterials regulates BMSCs differentiation via mechanical microenvironment

Biomaterials Advances, Journal Year: 2023, Volume and Issue: 157, P. 213738 - 213738

Published: Dec. 22, 2023

Language: Английский

---

The functional effects of Piezo channels in mesenchymal stem cells

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 26, 2023

Abstract Mesenchymal stem cells (MSCs) are widely used in cell therapy, tissue engineering, and regenerative medicine because of their self-renewal, pluripotency, immunomodulatory properties. The microenvironment which MSCs located significantly affects physiological functions. directly or indirectly behavior through biophysical, biochemical, other means. Among them, the mechanical signals provided to by have a particularly pronounced effect on functions can affect osteogenic differentiation, chondrogenic senescence MSCs. Mechanosensitive ion channels such as Piezo1 Piezo2 important transducing signals, these distributed sites skin, bladder, kidney, lung, sensory neurons, dorsal root ganglia. Although there been numerous studies Piezo recent years, function is still not well understood, has no summary relationship illustrate affected possible underlying mechanisms. Therefore, based members, structures, fundamental information MSCs, this paper focused summarizing advances from various sources provide new ideas for future research practical applications

Language: Английский

---

The role of mechanically sensitive ion channel Piezo1 in bone remodeling

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 8, 2024

Piezo1 (2010) was identified as a mechanically activated cation channel capable of sensing various physical forces, such tension, osmotic pressure, and shear force. mediates mechanosensory transduction in different organs tissues, including its role maintaining bone homeostasis. This review aimed to summarize the function possible mechanism mechanical receptor cells tissue. We found that it is potential therapeutic target for treatment diseases.

Language: Английский

---