Skeletal interoception in bone homeostasis and pain

Cell Metabolism, Год журнала: 2022, Номер 34(12), С. 1914 - 1931

Опубликована: Окт. 17, 2022

Язык: Английский

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Research Progress in Calcitonin Gene-Related Peptide and Bone Repair

Biomolecules, Год журнала: 2023, Номер 13(5), С. 838 - 838

Опубликована: Май 15, 2023

Calcitonin gene-related peptide (CGRP) has 37 amino acids. Initially, CGRP had vasodilatory and nociceptive effects. As research progressed, evidence revealed that the peripheral nervous system is closely associated with bone metabolism, osteogenesis, remodeling. Thus, bridge between skeletal muscle system. can promote inhibit resorption, vascular growth, regulate immune microenvironment. The G protein-coupled pathway vital for its effects, while MAPK, Hippo, NF-κB, other pathways have signal crosstalk, affecting cell proliferation differentiation. current review provides a detailed description of repair effects CGRP, subjected to several therapeutic studies, such as drug injection, gene editing, novel materials.

Язык: Английский

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M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 31, 2024

Abstract Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown significance M1-type macrophages in IVDD; nevertheless, precise mechanism route it influences function nucleus pulposus cell (NPC) remain unknown. Utilizing rat acupuncture model an NPC induced lipopolysaccharide (LPS), we investigated M1 macrophage-derived exosomes (M1-Exos) both vivo vitro this study. We found that M1-Exos enhanced LPS-induced senescence, increased number SA-β-gal-positive blocked cycle, promoted activation P21 P53. derived from supernatant pretreated with exosome inhibitor GW4869 reversed result vitro. RNA-seq showed Lipocalin2 (LCN2) was enriched targeted NF-κB pathway. The quantity cells significantly reduced inhibition LCN2, expression P53 NPCs decreased. same results were obtained acupuncture-induced model. In addition, LCN2 promotes type II collagen (Col-2) inhibits matrix metalloproteinase 13 (MMP13), thereby restoring equilibrium metabolism inside extracellular (ECM) vivo. pathway crucial for regulating M1-Exo-mediated senescence. After addition LPS-treated NPCs, p-p65 activity activated, while si-LCN2 treatment inhibited activity. Therefore, paper demonstrates ability deliver activates signaling pathway, exacerbates accelerating This shed new light on bring fresh approach therapy. Graphical

Язык: Английский

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Skeletal interoception in osteoarthritis

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Апрель 1, 2024

Abstract The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of organism. Among its various forms, skeletal specifically regulates bones. Osteoarthritis (OA) is a complex joint disorder involving cartilage, subchondral bone, synovium. bone undergoes continuous remodeling to adapt dynamic loads. Recent findings highlight that mediated aberrant mechanical loads contributes pathological resulting sclerosis OA. also potential mechanism for chronic synovial inflammation In this review, we offer general overview interoception, microenviroment remedeling. We discuss role abnormal OA, as well prospects challenges exploring novel OA therapies target interoception.

Язык: Английский

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Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Окт. 20, 2022

Ferroptosis, an iron-dependent form of programmed cell death marked by phospholipid peroxidation, is regulated complex cellular metabolic pathways including lipid metabolism, iron balance, redox homeostasis, and mitochondrial activity. Initial research regarding the mechanism ferroptosis mainly focused on solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (GPX4) signal pathway. Recently, novel mechanisms ferroptosis, independent GPX4, have been discovered. Numerous pathologies associated with extensive such as drug-resistant cancers, ischemic organ injuries, neurodegenerative diseases, are driven ferroptosis. Ferroptosis a new therapeutic target for intervention IVDD. The role in modulation intervertebral disc degeneration (IVDD) significant topic interest. This topic, IVDD ongoing. Herein, we aim to review discuss literature explore relationship between regulatory networks cells nucleus pulposus, annulus fibrosus, cartilage endplate provide references future basic clinical translation treatment.

Язык: Английский

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Sensory nerve regulation of bone homeostasis: Emerging therapeutic opportunities for bone-related diseases

Ageing Research Reviews, Год журнала: 2024, Номер 99, С. 102372 - 102372

Опубликована: Июнь 14, 2024

Язык: Английский

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Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

Pharmacological Reviews, Год журнала: 2022, Номер 75(1), С. 1 - 34

Опубликована: Дек. 8, 2022

G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent these interactions mechanisms effects not well understood. For example, one class GPCR-interacting proteins, receptor activity-modifying (RAMPs), comprise three related ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, since then GPCR-RAMP functional consequences on trafficking ligand selectivity have been documented for secretin (class B) GPCRs, most notably calcitonin receptor-like receptor. Recent bioinformatics multiplexed experimental studies suggest might be much widespread previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures GPCR-RAMP-ligand complexes, drugs developed target complexes. In this review, we provide a summary recent advances in techniques allow discovery highlight prospects future advances. We also an up-to-date list reported based review current literature. SIGNIFICANCE STATEMENT: Receptor (RAMPs) emerged as modulators many aspects (GPCR)biology application new methodologies study protein-protein suggests RAMPs GPCRs had known. These findings, especially when combined structural protein significant implications advancing GPCR-targeted drug understanding GPCR pharmacology, biology, regulation.

Язык: Английский

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Sensory Nerve Maintains Intervertebral Disc Extracellular Matrix Homeostasis Via CGRP/CHSY1 Axis

Advanced Science, Год журнала: 2022, Номер 9(30)

Опубликована: Сен. 1, 2022

Abstract Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical denervation IVD results loss water preserve molecule chondroitin sulfate (CS), reduction CS bio‐synthesis gene synthase 1 (CHSY1) expression, and dysregulated ECM IVD. Particularly, knockdown neuros calcitonin gene‐related peptide (CGRP) expression induces similar metabolic disorder compared to model, effect is abolished CHSY1 knockout mice. Furthermore, vitro evidence CGRP regulates nucleus pulposus cell synthesis via receptor component activity‐modifying protein (RAMP1) cyclic AMP response element‐binding (CREB) signaling. Therapeutically, local injection forskolin significantly attenuates degeneration progression mouse annulus fibrosus puncture model. Overall, these maintains CGRP/CHSY1 axis promotes repair, expands understanding concerning how links system, thus shedding light on future development novel therapeutical strategy degeneration.

Язык: Английский

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Understanding necroptosis and its therapeutic target for intervertebral disc degeneration

International Immunopharmacology, Год журнала: 2023, Номер 121, С. 110400 - 110400

Опубликована: Июнь 7, 2023

Язык: Английский

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Regulation of Bone by Mechanical Loading, Sex Hormones, and Nerves: Integration of Such Regulatory Complexity and Implications for Bone Loss during Space Flight and Post-Menopausal Osteoporosis

Biomolecules, Год журнала: 2023, Номер 13(7), С. 1136 - 1136

Опубликована: Июль 15, 2023

During evolution, the development of bone was critical for many species to thrive and function in boundary conditions Earth. Furthermore, also became a storehouse calcium that could be mobilized reproductive purposes mammals other species. The nature both needs during evolution context Earth has led complex regulatory mechanisms require integration optimization this tissue across lifespan. Three important variables include mechanical loading, sex hormones, innervation/neuroregulation. importance loading been target much research as appears subscribe “use it or lose it” paradigm. because post-menopausal osteoporosis risk fractures loss function, aspect regulation focused on differences regulation. advent space flight exposure microgravity renewed interest unique environment, which not have anticipated by expose new insights into Finally, body evidence emerged indicating neuroregulation is central maintaining function. However, there still more needed understand regarding how such are integrated lifespan maintain particularly walks upright. This review will attempt discuss these elements integrity propose further study delineate details better improve treatments those at integrity, state prolonged flight.

Язык: Английский

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