Genetic lineage tracing of targeted cell populations during enthesis healing.

Moser, Helen Laura; Doe, Anton P; Meier, Kristen; Garnier, Simon; Laudier, Damien; Akiyama, Haruhiko; Zumstein, Matthias; Galatz, Leesa M; Huang, Alice H (2018). Genetic lineage tracing of targeted cell populations during enthesis healing. Journal of orthopaedic research, 36(12), pp. 3275-3284. Wiley 10.1002/jor.24122

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Rotator cuff supraspinatus tendon injuries are clinically challenging due to the high rates of failure after surgical repair. One key limitation to functional healing is the failure to regenerate the enthesis transition between tendon and bone, which heals by disorganized scar formation. Using two models of supraspinatus tendon injury in mouse (partial tear and full detachment/repair), the purpose of the study was to determine functional gait outcomes and identify the origin of the cells that mediate healing. Consistent with previous reports, enthesis injuries did not regenerate; partial tear resulted in a localized scar defect adjacent to intact enthesis, while full detachment with repair resulted in full disruption of enthesis alignment and massive scar formation between tendon and enthesis fibrocartilage. Although gait after partial tear injury was largely normal, gait was permanently impaired after full detachment/repair. Genetic lineage tracing of intrinsic tendon and cartilage/fibrocartilage cells (Scx and Sox9 , respectively), myofibroblasts (αSMA ), and Wnt-responsive stem cells (Axin2 ) failed to identify scar-forming cells in partial tear injury. Unmineralized enthesis fibrocartilage was strongly labeled by Sox9 while Axin2 labeled a subset of tendon cells away from the skeletal insertion site. In contrast to the partial tear model, Axin2 labeling showed considerable contribution of Axin2 cells to the scar after full detachment/repair. Clinical Significance: Clinically relevant models of rotator cuff tendon injuries in mouse enable the use of genetic tools; lineage tracing suggests that distinct mechanisms of healing are activated with full detachment/repair injuries versus partial tear. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3275-3284, 2018.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery

UniBE Contributor:

Moser, Helen Laura and Zumstein, Matthias

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0736-0266

Publisher:

Wiley

Language:

English

Submitter:

Kathrin Aeschlimann

Date Deposited:

15 Jul 2019 15:29

Last Modified:

24 Oct 2019 04:07

Publisher DOI:

10.1002/jor.24122

PubMed ID:

30084210

Uncontrolled Keywords:

enthesis healing injury rotator cuff tendon

BORIS DOI:

10.7892/boris.131537

URI:

https://boris.unibe.ch/id/eprint/131537

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