Limb proportions show developmental plasticity in response to embryo movement

Scientific Reports, Journal Year: 2017, Volume and Issue: 7(1)

Published: Feb. 6, 2017

Abstract Animals have evolved limb proportions adapted to different environments, but it is not yet clear what extent these are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested hypothesis that environmentally-induced changes in movement influence embryonic growth alter proportions. show incubation temperature influences motility and bone West African Dwarf crocodiles, producing altered which may, post-hatching performance. Pharmacological immobilisation of chickens revealed motility, independent temperature, may underpin this regulation. Use chick also allowed us merge histological, immunochemical cell proliferation labelling studies evaluate plate organisation, unbiased array profiling identify specific cellular transcriptional targets This disclosed alters regulates chondrocyte only plates. selective targeting related intrinsic mTOR (mechanistic target rapamycin) pathway activity individual Our findings provide new insights into how environmental factors can be integrated growing bones ultimately gross morphology, generate phenotypic variation

Language: Английский

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BMP signalling in skeletal development, disease and repair

Nature Reviews Endocrinology, Journal Year: 2016, Volume and Issue: 12(4), P. 203 - 221

Published: Feb. 19, 2016

Language: Английский

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A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation

Development, Journal Year: 2015, Volume and Issue: 142(5), P. 817 - 831

Published: Feb. 27, 2015

Decades of work have identified the signaling pathways that regulate differentiation chondrocytes during bone formation, from their initial induction mesenchymal progenitor cells to terminal maturation into hypertrophic chondrocytes. Here, we review how multiple molecules, mechanical signals and morphological cell features are integrated activate a set key transcription factors determine genetic program induces chondrogenesis chondrocyte differentiation. Moreover, describe recent findings regarding roles several in modulating proliferation growth plate, which is ‘engine’ elongation.

Language: Английский

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Cell volume change through water efflux impacts cell stiffness and stem cell fate

Proceedings of the National Academy of Sciences, Journal Year: 2017, Volume and Issue: 114(41)

Published: Sept. 25, 2017

Significance Cell volume is thought to be a well-controlled cellular characteristic, increasing as cell grows, while macromolecular density maintained. We report that can also change in response external physical cues, leading water influx/efflux, which causes significant changes subcellular density. This observed when cells spread out on substrate: Cells reduce their and increase molecular crowding due an accompanying efflux. Exploring this phenomenon further, we removed from mesenchymal stem through osmotic pressure found was sufficient alter differentiation pathway. Based these results, suggest chart different behavioral pathways by sensing/altering cytoplasmic influx/efflux.

Language: Английский

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Mechanical confinement regulates cartilage matrix formation by chondrocytes

Nature Materials, Journal Year: 2017, Volume and Issue: 16(12), P. 1243 - 1251

Published: Oct. 2, 2017

Language: Английский

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Cellular biology of fracture healing

Journal of Orthopaedic Research®, Journal Year: 2018, Volume and Issue: 37(1), P. 35 - 50

Published: Oct. 29, 2018

ABSTRACT The biology of bone healing is a rapidly developing science. Advances in transgenic and gene‐targeted mice have enabled tissue cell‐specific investigations skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during bone, several years prior, seminal publications reported definitively the primary tissues contributing forming cells regeneration were periosteum endosteum. While genetically modified animals offer incredible insights into temporal spatial importance various gene products, complexity rapidity healing—coupled with heterogeneity animal models—renders studies regenerative challenging. Herein, play key role will be reviewed extracellular mediators regulating their behavior discussed. We focus on recent explore novel roles inflammation healing, origins fates fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Language: Английский

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On being the right (cell) size

Science, Journal Year: 2015, Volume and Issue: 348(6236)

Published: May 14, 2015

Different animal cell types have distinctive and characteristic sizes. How a particular size is specified by differentiation programs physiology remains one of the fundamental unknowns in biology. In this Review, we explore evidence that individual cells autonomously sense specify their own size. We discuss possible mechanisms which size-sensing size-specification may take place. Last, physiological implications control: Why it important maintain size? develop these questions through examination current literature pose anticipate will guide field upcoming years.

Language: Английский

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Single-cell RNA-seq analysis reveals the progression of human osteoarthritis

Annals of the Rheumatic Diseases, Journal Year: 2018, Volume and Issue: 78(1), P. 100 - 110

Published: July 19, 2018

Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies treating osteoarthritis (OA). Here, we report programmes lineage progression patterns controlling OA pathogenesis using single-cell RNA sequencing (scRNA-seq).We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis histological assays on 1464 chondrocytes from 10 patients with undergoing knee arthroplasty surgery. We investigated relationship between transcriptional of landscape clinical outcome severity index correspondence analysis.We identified seven molecularly defined populations in cartilage, including three novel phenotypes distinct functions. presented gene expression profiles at different stages resolution. found a potential transition among proliferative chondrocytes, prehypertrophic hypertrophic (HTCs) new subdivision within HTCs. revealed markers progenitor cells (CPCs) demonstrated CPCs fibrocartilage analysis. Notably, derived predictive targets respect to outcomes clarified role cell types early diagnosis treatment OA.Our results provide insights into chondrocyte taxonomy present clues effective functional manipulation that could lead improved health.

Language: Английский

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Live-cell mass profiling: an emerging approach in quantitative biophysics

Nature Methods, Journal Year: 2014, Volume and Issue: 11(12), P. 1221 - 1228

Published: Nov. 25, 2014

Language: Английский

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Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes

Development, Journal Year: 2017, Volume and Issue: 144(2), P. 221 - 234

Published: Jan. 15, 2017

Fractures heal predominantly through the process of endochondral ossification. The classic model ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate transdifferentiate osteoblasts in growth plate during regeneration, yet mechanism(s) regulating this remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic at chondro-osseous border fracture callus, region define as transition zone (TZ). Hypertrophic TZ activate expression pluripotency factors [Sox2, Oct4 (Pou5f1), Nanog], conditional knock-out Sox2 healing results reduction callus delay conversion cartilage bone. signal(s) triggering genes are unknown, but endothelial cell conditioned medium upregulates these ex vivo cultures, supporting histological evidence transdifferentiation occurs adjacent vasculature. Elucidating cellular molecular mechanisms underlying repair is important for understanding why some fractures fail developing novel therapeutic interventions.

Language: Английский

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