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Citations to this article

Immobilization after injury alters extracellular matrix and stem cell fate
Amanda K. Huber, … , Aaron W. James, Benjamin Levi
Amanda K. Huber, … , Aaron W. James, Benjamin Levi
Published July 16, 2020
Citation Information: J Clin Invest. 2020;130(10):5444-5460. https://doi.org/10.1172/JCI136142.
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Research Article Bone biology Article has an altmetric score of 67

Immobilization after injury alters extracellular matrix and stem cell fate

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Abstract

Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO.

Authors

Amanda K. Huber, Nicole Patel, Chase A. Pagani, Simone Marini, Karthik R. Padmanabhan, Daniel L. Matera, Mohamed Said, Charles Hwang, Ginny Ching-Yun Hsu, Andrea A. Poli, Amy L. Strong, Noelle D. Visser, Joseph A. Greenstein, Reagan Nelson, Shuli Li, Michael T. Longaker, Yi Tang, Stephen J. Weiss, Brendon M. Baker, Aaron W. James, Benjamin Levi

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 Total
Citations: 5 6 10 15 3 1 40
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2023 (10)

Title and authors Publication Year
Itaconate-producing neutrophils regulate local and systemic inflammation following trauma
Robert Tower, Janna Crossley, Sonya Ostashevskaya-Gohstand, Stefano Comazzetto, Jessica Hook, Lei Guo, Neda Vishlaghi, Conan Juan, Lin Xu, Alexander Horswill, Gerta Hoxhaj, Jessica Moreland, Benjamin Levi
JCI Insight 2023
Influence of PHA Substrate Surface Characteristics on the Functional State of Endothelial Cells.
Ryltseva GA, Dudaev AE, Menzyanova NG, Volova TG, Alexandrushkina NA, Efimenko AY, Shishatskaya EI
Journal of Functional Biomaterials 2023
Heterotopic mineral deposits in intact rat Achilles tendons are characterized by a unique fiber-like structure
Pierantoni M, Hammerman M, Silva Barreto I, Andersson L, Novak V, Isaksson H, Eliasson P
2023
Engineering Cell–ECM–Material Interactions for Musculoskeletal Regeneration
Jones CL, Penney BT, Theodossiou SK
Bioengineering 2023
Adult tissue-specific stem cell interaction: novel technologies and research advances
Luo X, Liu Z, Xu R
Frontiers in Cell and Developmental Biology 2023
Preclinical Tendon and Ligament Models: Beyond the 3Rs (Replacement, Reduction, and Refinement) to 5W1H (Why, Who, What, Where, When, How)
Little D, Amadio PC, Awad H, Cone SG, Dyment NA, Fisher MB, Huang AH, Koch DW, Kuntz AF, Madi R, McGilvrey K, Schnabel LV, Shetye SS, Thomopoulos S, Zhao C, Soslowsky LJ
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2023
Effect of mechanical stimulation on tissue heterotopic ossification: an in vivo experimental study
Zhu Z, He Z, Tang T, Wang F, Chen H, Zhou J, Lin C, Chen G, Wang J, Li J, Liu X, Zhou Z, Liu S
Frontiers in physiology 2023
Ultrasound-Driven Healing: Unleashing the Potential of Chondrocyte-Derived Extracellular Vesicles for Chondrogenesis in Adipose-Derived Stem Cells
Wang Y, Liu Z, Pan C, Zheng Y, Chen Y, Lian X, Jiang Y, Chen C, Xue K, Zhang Y, Xu P, Liu K
Biomedicines 2023
Neutrophil and NETosis modulation in traumatic heterotopic ossification
Nunez JH, Juan C, Sun Y, Hong J, Bancroft AC, Hwang C, Medrano J, Huber AK, Tower RJ, Levi B
Annals of Surgery 2023
Enhanced BMP signaling in Cathepsin K-positive tendon progenitors induces heterotopic ossification.
Yamaguchi H, Li M, Kitami M, Swaminathan S, Mishina Y, Komatsu Y
Biochemical and Biophysical Research Communications 2023

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