Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues.

Autor:	Heo SJ; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA USA., Song KH; Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA USA.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA., Thakur S; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Miller LM; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA., Cao X; Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA USA.; Department of Materials Science Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA., Peredo AP; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA., Seiber BN; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA., Qu F; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA., Driscoll TP; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA., Shenoy VB; Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA USA.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Department of Materials Science Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA., Lakadamyali M; Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA USA.; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Burdick JA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA USA.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA., Mauck RL; McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA USA.; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Jun 19; Vol. 6 (25), pp. eaax5083. Date of Electronic Publication: 2020 Jun 19 (Print Publication: 2020).
DOI:	10.1126/sciadv.aax5083
Abstrakt:	Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we interrogated the interstitial migratory capacity of adult meniscal cells through dense fibrous networks and adult tissue before and after nuclear softening via the application of a histone deacetylase inhibitor, Trichostatin A (TSA) or knockdown of the filamentous nuclear protein Lamin A/C. Our results show that transient softening of the nucleus improves migration through microporous membranes, electrospun fibrous matrices, and tissue sections and that nuclear properties and cell function recover after treatment. We also showed that biomaterial delivery of TSA promoted in vivo cellularization of scaffolds by endogenous cells. By addressing the inherent limitations to repair imposed by nuclear stiffness, this work defines a new strategy to promote the repair of damaged dense connective tissues. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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