دورية أكاديمية
Computational and experimental characterizations of the spatiotemporal activity and functional role of TGF-β in the synovial joint.
| العنوان: | Computational and experimental characterizations of the spatiotemporal activity and functional role of TGF-β in the synovial joint. |
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| المؤلفون: | Dogru S; Department of Mechanical Engineering, Boston University, United States., Dai Z; Department of Biomedical Engineering, Boston University, United States., Alba GM; Department of Biomedical Engineering, Boston University, United States., Simone NJ; Department of Biomedical Engineering, Boston University, United States., Albro MB; Department of Mechanical Engineering, Boston University, United States; Department of Biomedical Engineering, Boston University, United States; Division of Materials Science & Engineering, Boston University, United States. Electronic address: albro@bu.edu. |
| المصدر: | Journal of biomechanics [J Biomech] 2023 Jul; Vol. 156, pp. 111673. Date of Electronic Publication: 2023 Jun 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 0157375 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2380 (Electronic) Linking ISSN: 00219290 NLM ISO Abbreviation: J Biomech Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York ; Oxford : Elsevier Science |
| مواضيع طبية MeSH: | Transforming Growth Factor beta*/pharmacology , Cartilage, Articular*/metabolism, Joints ; Cartilage/metabolism ; Synovial Membrane/metabolism ; Chondrocytes ; Synovial Fluid/metabolism |
| مستخلص: | TGF-β is a prominent anabolic signaling molecule associated with synovial joint health. Recent work has uncovered mechanochemical mechanisms that activate the latent form of TGF-β (LTGF-β) in the synovial joint-synovial fluid (SF) shearing or cartilage compression-pointing to mechanobiological phenomena, whereby enhanced TGF-β activity occurs during joint stimulation. Here, we implement computational and experimental models to better understand the role of mechanochemical-activated TGF-β (aTGF-β) in regulating the functional biosynthetic activities of synovial joint tissues. Reaction-diffusion models describe the pronounced role of extracellular chemical reactions-load-induced activation, reversible ECM-binding, and cell-mediated internalization-in modulating the spatiotemporal distribution of aTGF-β in joint tissues. Of note, aTGF-β from SF shearing predominantly acts on cells in peripheral tissue regions (superficial zone [SZ] chondrocytes and synoviocytes) and aTGF-β from cartilage compression acts on chondrocytes through all cartilage layers. Further, ECM reversible binding sites in cartilage act to modulate the temporal delivery of aTGF-β to cells, creating a dynamic where short durations of joint activity give rise to extended periods of aTGF-β exposure at moderated doses. Ex vivo tissue models were subsequently utilized to characterize the influence of physiologic aTGF-β activity regimens in regulating functional biosynthetic activities. Physiologic exposure regimens of aTGF-β in SF induce strong 4-fold to 9-fold enhancements in the secretion rate of the synovial biolubricant, PRG4, from SZ cartilage and synovium explants. Further, aTGF-β inhibition in cartilage over 1-month culture leads to a pronounced loss of GAG content (30-35% decrease) and tissue softening (60-65% E Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Ltd. All rights reserved.) |
| معلومات مُعتمدة: | S10 OD024993 United States OD NIH HHS |
| فهرسة مساهمة: | Keywords: Cartilage mechanobiology; Growth factor transport modeling; Lubricin; Proteoglycan-4; TGF-beta activation |
| المشرفين على المادة: | 0 (Transforming Growth Factor beta) |
| تواريخ الأحداث: | Date Created: 20230626 Date Completed: 20230710 Latest Revision: 20230718 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.jbiomech.2023.111673 |
| PMID: | 37364394 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1873-2380 |
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| DOI: | 10.1016/j.jbiomech.2023.111673 |