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., Dudhia, J., & 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
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.3390/ijms22189729
• Public URL: https://rvc-repository.worktribe.com/output/1550260