Purpose
To evaluate the altered gene and protein expression patterns in the rotator cuff muscles
of smokers and non-smokers with rotator cuff tears and to identify the smoking-associated
key genetic factor(s) involved in rotator cuff muscle physiology.
Methods
Twenty-four samples of rotator cuff muscle from 12 current heavy smokers (mean age
61.8 ± 5.1 years) and age- and sex-matched 12 non-smokers (mean age 61.8 ± 6.9 years)
with medium-sized tears were acquired during arthroscopic surgery. As a statistical
method, the propensity score matching technique was used to select control group by
1:1 matching for age and sex. Inclusion criteria were patients who underwent arthroscopic
repair for medium-sized full-thickness rotator cuff tears and those that were current
smokers with a smoking history >20 packs/year. Patients lacking medium-sized tears,
those with recent steroid injection history, isolated subscapularis tear, preoperative
stiff shoulder, acute traumatic tear, or previous surgery on the same shoulder, or
those that declined to participate were excluded. Alterations in the expression of
genes and proteins associated with myogenesis, inflammation, adipogenesis, and muscle
fibrosis were compared between smokers and non-smokers with reverse-transcription
quantitative polymerase chain reaction, western blotting, and immunohistochemistry.
Results
Histologic analysis revealed increased inflammation and remarkable fat accumulation
and fibrogenesis in the rotator cuff muscle from smokers compared with that from non-smokers.
The mRNA expression levels of inflammatory high mobility group box 1 (HMGB1; P = .043), adipogenic CCAAT/enhancer-binding protein alpha (P = .046) and peroxisome proliferator-activated receptor gamma (PPARγ; P = .048), myogenic differentiation 1 (P = .032), fibrogenic alpha-smooth muscle actin (α-SMA; P = .033), and metalloproteinase 9 (P = .036) were significantly greater in samples from smokers than from non-smokers.
A correlation was observed between gene and protein expression of HMGB1 (P = .034), PPARγ (P = .021), and α-SMA (P = .021).
Conclusions
Smokers with rotator cuff tears showed high inflammation, large fat infiltration,
and fibrosis in rotator cuff muscle that is associated with the increased expression
of HMGB1, PPARγ, and α-SMA, respectively.
Level of Evidence
Case control study (Prognostic level III)
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Article info
Publication history
Accepted:
June 21,
2019
Received:
December 24,
2018
Footnotes
See commentary on page 3192
The authors report the following potential conflicts of interest or sources of funding: this study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017R1D1A1B03033758 to Y.-S.L. and NRF-2017R1A2B4003343 to S.W.C.). Full ICMJE author disclosure forms are available for this article online, as supplementary material.
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© 2019 by the Arthroscopy Association of North America
ScienceDirect
Access this article on ScienceDirectLinked Article
- Editorial Commentary: Bad For Your Cuff. Smoking Causes Alterations in Gene Expression Resulting in Inflammation, Fatty Degeneration, and Fibrosis. Or Maybe Not?ArthroscopyVol. 35Issue 12
- PreviewGene expression is the transcription from DNA to RNA and then translation into proteins or other mediators. Smoking causes alterations in gene expression and can result in inflammatory changes, fatty degeneration, and fibrosis in patients with rotator cuff disease. Whether the smoking-related upregulation of inflammatory mediators such as interleukin 6 and C-reactive protein is one of the responsible factors for rotator cuff tears and also influences healing after surgery is currently not known.
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