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; Fang, Yongxiang; Peffers, Mandy; Pitsillides, Andrew; Dudhia, Jayesh; Thorpe, Chavaunne

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. Results demonstrated the formation of a focal lesion at the injury site that increased in size and cellularity up to 21 days post-injury. In healthy tendon, CD146+ cells localised to the IFM, and with injury, CD146+ cells migrated towards the lesion at days 4 and 7, and remained within 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 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.

Citation

Marr, N., Meeson, R., Kelly, E., Fang, Y., Peffers, M., Pitsillides, A., …Thorpe, C. (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, https://doi.org/10.3390/ijms22189729

• Journal Article Type: Article
• Acceptance Date: Sep 5, 2021
• Publication Date: Sep 8, 2021
• Deposit Date: Sep 8, 2021
• Publicly Available Date: Nov 11, 2021
• Print ISSN: 1661-6596
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.3390/ijms22189729
• Public URL: https://rvc-repository.worktribe.com/output/1550260