Emerging pharmaceutical therapies for osteoarthritis

Nature Reviews Rheumatology, Journal Year: 2020, Volume and Issue: 16(12), P. 673 - 688

Published: Oct. 29, 2020

Language: Английский

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Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis

Nature Reviews Rheumatology, Journal Year: 2017, Volume and Issue: 13(12), P. 719 - 730

Published: Nov. 9, 2017

Language: Английский

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Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

Advanced Functional Materials, Journal Year: 2020, Volume and Issue: 30(44)

Published: Feb. 19, 2020

Abstract Bone is a hard yet dynamic tissue with remarkable healing capacities. Research to date has greatly advanced the understanding of how bone heals and led marked success in treatment injuries. Nevertheless, effective nonunions large defects continues present challenge for orthopedic surgeons. Biomaterials provide researchers powerful instrument potentially guide regeneration challenging environments. However, most appropriate biomaterial engineering be an area intense debate. Indeed, mechanical properties real can reproduced vitro but development functional substitute goes beyond sole properties. The faithful reproduction as organ requires combination different cell types temporal regulation molecular signaling involved during stages formation regeneration. This not at all trivial task. Herein, critical aspects healing/regeneration including loading, inflammation, vascularization, innervation are described. challenges behind biomaterials, technologies used functionalize them, order support underlying cellular mechanisms also highlighted.

Language: Английский

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Fracture repair requires TrkA signaling by skeletal sensory nerves

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(12), P. 5137 - 5150

Published: Oct. 21, 2019

Bone is richly innervated by nerve growth factor–responsive (NGF-responsive) tropomyosin receptor kinase A–expressing (TrKa-expressing) sensory fibers, which are required for osteochondral progenitor expansion during mammalian skeletal development. Aside from pain sensation, little known regarding the role of innervation in bone repair. Here, we characterized reinnervation tissue following experimental ulnar stress fracture and assessed impact loss TrkA signaling this process. Sequential histological data obtained reporter mice subjected to demonstrated a marked upregulation NGF expression periosteal stromal progenitors fracture-associated macrophages. Sprouting arborization CGRP+TrkA+ fibers within reactive periosteum NGF-enriched cellular domains were evident at time points preceding vascularization, ossification, mineralization. Temporal inhibition catalytic activity administration 1NMPP1 TrkAF592A significantly reduced numbers blunted revascularization, delayed ossification callus. We observed similar deficiencies regrowth healing mouse model peripheral neuropathy induced paclitaxel treatment. Together, our studies demonstrate an essential repair implicate nerves as important upstream mediator

Language: Английский

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Impact of the Autonomic Nervous System on the Skeleton

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(3), P. 1083 - 1112

Published: May 2, 2018

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

Language: Английский

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Nerves in Bone: Evolving Concepts in Pain and Anabolism

Journal of Bone and Mineral Research, Journal Year: 2019, Volume and Issue: 34(8), P. 1393 - 1406

Published: June 27, 2019

ABSTRACT The innervation of bone has been described for centuries, and our understanding its function rapidly evolved over the past several decades to encompass roles subtype‐specific neurons in skeletal homeostasis. Current research largely focused on distribution specific neuronal populations within bone, as well their cellular molecular relationships with target cells microenvironment. This review provides a historical perspective field neurobiology that highlights diverse yet interconnected nature nerves health, particularly context anabolism pain. We explore what is known regarding subtypes found skeleton, compartments, central projection pathways. neuroskeletal map then serves foundation comprehensive discussion neural control development, homeostasis, repair, Active synthesis this recently led first biotherapeutic success story field. Specifically, ongoing clinical trials anti‐nerve growth factor therapeutics have optimized titrated doses effectively alleviate pain while maintaining joint health. Continued collaborations between neuroscientists biologists are needed build progress, leading more complete regulation skeleton development novel therapeutics. © 2019 Authors. Journal Bone Mineral Research published by Wiley Periodicals, Inc.

Language: Английский

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Functionalized 3D-printed silk-hydroxyapatite scaffolds for enhanced bone regeneration with innervation and vascularization

Biomaterials, Journal Year: 2021, Volume and Issue: 276, P. 120995 - 120995

Published: July 1, 2021

Language: Английский

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Crosstalk between Bone and Nerves within Bone

Advanced Science, Journal Year: 2021, Volume and Issue: 8(7)

Published: Feb. 10, 2021

Abstract For the past two decades, function of intrabony nerves on bone has been a subject intense research, while is still hidden in corner. In present review, possible crosstalk between and peripheral will be comprehensively analyzed. Peripheral participate development repair via host signals generated through secretion neurotransmitters, neuropeptides, axon guidance factors neurotrophins, with additional contribution from nerve‐resident cells. return, contributes to this microenvironmental rendezvous by housing within its internal milieu provide mechanical support protective shelf. A large ensemble chemical, mechanical, electrical cues works harmony marrow stromal cells regulation nerves. The not limited physiological state, but also involved various diseases including osteoporosis, osteoarthritis, heterotopic ossification, psychological stress‐related abnormalities, related tumors. This may harnessed design tissue engineering scaffolds for defects or targeted treatment

Language: Английский

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Neurovascular coupling in bone regeneration

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(11), P. 1844 - 1849

Published: Nov. 29, 2022

Abstract The mammalian skeletal system is densely innervated by both neural and vascular networks. Peripheral nerves in the skeleton include sensory sympathetic nerves. crosstalk between tissues critical for development regeneration. cellular processes of osteogenesis angiogenesis are coupled physiological pathophysiological contexts. molecular regulation have yet to be fully defined. This review will provide a detailed characterization regulatory role blood vessels during bone Furthermore, given importance spatial relationship bone, we discuss neurovascular coupling pathological formation. A better understanding interactions inform future novel therapeutic targeting clinical repair

Language: Английский

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Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 2, 2024

Abstract The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This process plays a crucial role in bone formation and homeostasis is regulated by two intricate processes: cell signal transduction transcriptional gene expression. Various essential signaling pathways, including Wnt, BMP, TGF-β, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, Piezo1/2, play critical facilitating osteoblast differentiation, formation, homeostasis. Key factors this include Runx2, Cbfβ, Runx1, Osterix, ATF4, SATB2, TAZ/YAP. Furthermore, diverse array epigenetic also roles at the level. review provides an overview latest developments current comprehension concerning pathways signaling, regulation hormones, genes involved commitment lineage, well maintenance paper reviews via mechanisms, such histone DNA modifications. Additionally, we summarize biology spurred recent advancements various modern technologies bioinformatics. By synthesizing these insights comprehensive understanding further clarification mechanisms underlying lineage commitment, highlights potential new therapeutic applications for treatment diseases.

Language: Английский

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