Josiah Brown Poster Abstract

Archive

Ajith K. Subhash
Frank A. Petrigliano, M.D.
Ben Van Handel, Ph.D., Ascia Eskin, M.S., Allison Ariniello, B.S., Sai Devana, M.D., Abhinav K. Sharma, B.S., Gina Mosich, M.D., Bruno Peault, Ph.D., Ayelet Dar, Ph.D., Frank A. Petrigliano, M.D.
Molecular Characterization of Fibroadipogenesis and Transient Myogenesis in a Murine Model of Massive Rotator Cuff Tear
STTP

Rotator cuff tears (RCTs) are one of the most common shoulder injuries and often result in reduced mobility, shoulder pain, and diminished quality of life (1). Despite advances in surgical technique, the failure rate of rotator cuff repair ranges between 11%-94% (2-5). A major reason for these post-operative failures is due to muscle atrophy and fatty degeneration, which lead to decreased muscle compliance and may compromise the repair (6-8).

This has prompted research into characterizing the stage-specific changes in gene expression of remodeling RC following massive tears. The purpose of our study is to evaluate the temporal changes in gene expression and understand the molecular underpinnings of fibroadipogenesis and muscle atrophy following RC injury. We used a murine model of irreversible tendon and nerve transection (TTDN) that recapitulates the degenerative fibroadipogenesis and atrophy of the shoulder muscle consecutive to massive chronic tears. RNA-sequencing was performed to identify differences in gene expression in injured murine RC tissues at 5 days, 2 weeks, and 6 weeks post TTDN compared to non-injured RC (N=3 mice per group). 84 genes were queried, and heat maps are currently being generated to identify differential gene expression. Additional genes will be queried and a functional analysis will be performed to investigate the effects that these genes may have in RC remodeling.

Identifying vast array of mRNAs following tendon and nerve injury may enable identification of candidate therapeutic molecules for target therapy that will potentially improve surgical outcomes post-RCT.

References

1) Cofield RH, Parvizi J, Hoffmeyer PJ, Lanzer WL, Ilstrup DM, Rowland CM. Surgical repair of chronic rotator cuff tears. A prospective long-term study. J Bone Joint Surg Am. 2001 Jan;83(1):71-7. 4.

2) Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am. 2004 Feb;86(2):219-24.

3) Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM, Krishnan SG. Arthroscopic repair of full-thickness tears of the supraspinatus: does the tendon really heal? J Bone Joint Surg Am. Jun 2005;87(6):1229-1240.

4) Gerber C, Fuchs B, Hodler J. The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am. Apr 2000;82(4):505-515.

5) Levy O, Venkateswaran B, Even T, Ravenscroft M, Copeland S. Mid-term clinical and sonographic outcome of arthroscopic repair of the rotator cuff. J Bone Joint Surg Br. Oct 2008;90(10):1341-1347.

6) Burkhart SS, Barth JR, Richards DP, Zlatkin MB, Larsen M. Arthroscopic repair of massive rotator cuff tears with stage 3 and 4 fatty degeneration. Arthroscopy. Apr 2007;23(4):347-354.

7) Cofield RH, Parvizi J, Hoffmeyer PJ, Lanzer WL, Ilstrup DM, Rowland CM. Surgical repair of chronic rotator cuff tears. A prospective long-term study. J Bone Joint Surg Am. Jan 2001;83-A(1):71-77.

8) Gartsman GM. Massive, irreparable tears of the rotator cuff. Results of operative debridement and subacromial decompression. J Bone Joint Surg Am. May 1997;79(5):715-721

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