Investigating the temporal roles of decorin and biglycan in tendon healing.

Autor:	Leahy TP; Department of Orthopaedic Surgery, McKay Orthopaedic Laboratory, University of Pennsylvania, Pennsylvania, Philadelphia, USA.; Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Fung AK; Department of Orthopaedic Surgery, McKay Orthopaedic Laboratory, University of Pennsylvania, Pennsylvania, Philadelphia, USA.; Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Weiss SN; Department of Orthopaedic Surgery, McKay Orthopaedic Laboratory, University of Pennsylvania, Pennsylvania, Philadelphia, USA., Dyment NA; Department of Orthopaedic Surgery, McKay Orthopaedic Laboratory, University of Pennsylvania, Pennsylvania, Philadelphia, USA.; Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Soslowsky LJ; Department of Orthopaedic Surgery, McKay Orthopaedic Laboratory, University of Pennsylvania, Pennsylvania, Philadelphia, USA.; Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Journal of orthopaedic research : official publication of the Orthopaedic Research Society [J Orthop Res] 2023 Oct; Vol. 41 (10), pp. 2238-2249. Date of Electronic Publication: 2023 May 13.
DOI:	10.1002/jor.25590
Abstrakt:	The small leucine-rich proteoglycans, decorin and biglycan, are minor components of the tendon extracellular matrix that regulate fibrillogenesis and matrix assembly. Our study objective was to define the temporal roles of decorin and biglycan during tendon healing using inducible knockout mice to include genetic knockdown at specific phases of healing: time of injury, the proliferative phase, and the remodeling phase. We hypothesized that knockdown of decorin or biglycan would adversely affect tendon healing, and that by prescribing the timing of knockdown, we could elucidate the temporal roles of these proteins during healing. Contrary to our hypothesis, decorin knockdown did not affect tendon healing. However, when biglycan was knocked down, either alone or coupled with decorin, tendon modulus was increased relative to wild-type mice, and this finding was consistent among all induction timepoints. At 6 weeks postinjury, we observed increased expression of genes associated with the extracellular matrix and growth factor signaling in the biglycan knockdown and compound decorin-biglycan knockdown tendons. Interestingly, these groups demonstrated opposing trends in gene expression as a function of knockdown-induction timepoint, highlighting distinct temporal roles for decorin and biglycan. In summary, this study finds that biglycan plays multiple functions throughout tendon healing, with the most impactful, detrimental role likely occurring during late-stage healing. Statement of clinical importance: This study helps to define the molecular factors that regulate tendon healing, which may aid in the development of new clinical therapies. (© 2023 Orthopaedic Research Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text