CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4

Marr, Neil, Meeson, Richard, Kelly, Elizabeth F, Fang, Yongxiang ORCID: 0000-0002-4514-5292, Peffers, Mandy J ORCID: 0000-0001-6979-0440, Pitsillides, Andrew A, Dudhia, Jayesh and Thorpe, Chavaunne T (2021) CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (18). 9729-.

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Official URL: http://dx.doi.org/10.3390/ijms22189729

Abstract

The interfascicular matrix (IFM) binds tendon fascicles and contains a population of morphologically distinct cells. However, the role of IFM-localised cell populations in tendon repair remains to be determined. The basement membrane protein laminin-α4 also localises to the IFM. Laminin-α4 is a ligand for several cell surface receptors, including CD146, a marker of pericyte and progenitor cells. We used a needle injury model in the rat Achilles tendon to test the hypothesis that the IFM is a niche for CD146+ cells that are mobilised in response to tendon damage. We also aimed to establish how expression patterns of circulating non-coding RNAs alter with tendon injury and identify potential RNA-based markers of tendon disease. The results demonstrate the formation of a focal lesion at the injury site, which increased in size and cellularity for up to 21 days post injury. In healthy tendon, CD146+ cells localised to the IFM, compared with injury, where CD146+ cells migrated towards the lesion at days 4 and 7, and populated the lesion 21 days post injury. This was accompanied by increased laminin-α4, suggesting that laminin-α4 facilitates CD146+ cell recruitment at injury sites. We also identified a panel of circulating microRNAs that are dysregulated with tendon injury. We propose that the IFM cell niche mediates the intrinsic response to injury, whereby an injury stimulus induces CD146+ cell migration. Further work is required to fully characterise CD146+ subpopulations within the IFM and establish their precise roles during tendon healing.

Item Type:	Article
Uncontrolled Keywords:	interfascicular matrix, tendon injury, CD146, LAMA4, Achilles tendon
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	20 Sep 2021 10:15
Last Modified:	17 Oct 2023 10:05
DOI:	10.3390/ijms22189729
Open Access URL:	https://doi.org/10.3390/ijms22189729
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3137686