Apoptosis and rotator cuff tears: scientific evidence from basic science to clinical findings

Osti, Leonardo; Buda, Matteo; Buono, Angelo Del; Osti, Raffaella; Massari, Leo; Maffulli, Nicola

doi:10.1093/bmb/ldx008

Cited by 21 publications

(23 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The skeletal anatomy’s potential importance on the genesis of rotator cuff tear has been studied for decades and remains a controversial subject. Recently, tendon degeneration (age-related or degeneration induced by genetics and medical conditions) seems to be the most credited theory for cuff rupture [ 14 – 17 ]. The origin of RCT is represented by an area of the tendon within a few mm of its insertion characterized by relative hypovascularization [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Nuclear lamin A in rotator cuff tear margin tenocytes: an antiapoptotic and cell mechanostat factor

et al. 2021

View full text Add to dashboard Cite

Background The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamin. A- and B-type lamins are the major components of the nuclear lamina. Lamins function in many nuclear activities. The role of lamin A and transcription factors (NF-kB) as anti-apoptotic is well documented. Recently, lamin A has also been considered as a mechanosensor protein that is able to maintain nuclear integrity from mechanical insults. We aimed to verify how lamin A expression varies in healthy cuff cells and in those with different-sized tears where various mechanical stresses are present. Methods Forty-three patients with rotator cuff tear (RCT) [23M–20F, mean age (SD): 63.5 (6.1)] were enrolled. Tissue samples excised from the most medial point of tear margins were analyzed for lamin A expression by immunohistochemistry. Controls were represented by samples obtained by normal supraspinatus tendons excised from patients submitted to reverse shoulder prosthesis implant [8M–7F, mean age (SD): 67.9 (7.1)]. The intensity of staining was graded, and an H-score was assigned. Statistical analysis was performed. Results Our study revealed a moderate intensity of lamin A in the healthy cuff tendons, a higher expression of this protein in the small tears, and a significant decrease of lamin A with increasing tear size (p < 0.0001). Conclusions Our study emphasizes the importance of early repair of small RCTs since nuclear stability is maintained, and the cellular function is protected by lamin A overexpression. High re-tear of massive cuff repair could be due to cellular apoptosis and nuclear modifications induced by lamin A lack. Level of evidence III

show abstract

Section: Discussionmentioning

confidence: 99%

Nuclear lamin A in rotator cuff tear margin tenocytes: an antiapoptotic and cell mechanostat factor

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, failure in rotator cuff healing remains one of the most common and well-known complications of surgical repair [3, 4]. Several factors associated with rotator cuff muscle changes, such as aging [5], apoptosis [6], muscle degeneration [7], sarcopenia [8], muscle atrophy [9], and muscle fatty infiltration [10], have been demonstrated to be associated with rotator cuff tear. Further, these anatomical and physiological rotator cuff muscle changes reportedly result in healing failure and poor functional outcomes after rotator cuff repair [11–13].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Patterns Analysis in the Supraspinatus Muscle after a Rotator Cuff Tear in a Mouse Model

Lee

Kim

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Rotator cuff tear is a muscle-tendinous injury representative of various musculoskeletal disorders. In general, rotator cuff tear occurs in the tendon, but it causes unloading of the muscle resulting in muscle degeneration including fatty infiltration. These muscle degenerations lead to muscle weakness, pain, and loss of shoulder function and are well known as important factors for poor functional outcome after rotator cuff repair. Given that rotator cuff tear in various animal species results in similar pathological changes seen in humans, the animal model can be considered a good approach to understand the many aspects of the molecular changes in injured muscle. To comprehensively analyze changes in gene expression with time following a rotator cuff tear, we established a rotator cuff tear in mouse supraspinatus tendon of shoulder. At weeks 1 and 4 after the tear, the injured muscles were harvested for RNA isolation, and microarray analysis was performed. Expression patterns of genes belonging to 10 muscle physiology-related categories, including aging, apoptosis, atrophy, and fatty acid transport, were analyzed and further validated using real-time PCR. A total of 39,429 genes were analyzed, and significant changes in expression were observed for 12,178 genes at 1 week and 2,370 genes at 4 weeks after the tear. From the list of top 10 significantly up- and downregulated genes at the 2 time periods and the network evaluation of relevant genes according to the 10 categories, several important genes in each category were observed. In this study, we found that various genes are significantly altered after rotator cuff tear, and these genes may play key roles in controlling muscle degeneration after a rotator cuff tear.

show abstract

“…Apoptosis of tendon cells has also been considered to be the hallmark for RCI pathology which involves mitochondrial pathways 36 . Even though the tenocytes are resistant to transient hypoxia, the persistent hypoxia drives apoptosis of the tenocytes following RCI in response to inflammatory cytokines 37 . Consequently, a disturbance in tendon matrix homeostasis due to the switch of collagen synthesis from Collagen I to Collagen III occurs which is responsible for the loss of mechanical integrity and subsequent tendon function 37 .…”

Section: Discussionmentioning

confidence: 99%

“…Even though the tenocytes are resistant to transient hypoxia, the persistent hypoxia drives apoptosis of the tenocytes following RCI in response to inflammatory cytokines 37 . Consequently, a disturbance in tendon matrix homeostasis due to the switch of collagen synthesis from Collagen I to Collagen III occurs which is responsible for the loss of mechanical integrity and subsequent tendon function 37 . Recently, we reported the impact of phenotype switch from collagen type I to type III in the biceps tendon tissues of human RCI patients 29 , 38 and also in animal models 19 .…”

Section: Discussionmentioning

confidence: 99%

Amplification of Mitochondrial Activity in the Healing Response Following Rotator Cuff Tendon Injury

Thankam

Chandra

Kovilam

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Mitochondrial function following rotator cuff tendon injury (RCI) influences the tendon healing. We examined the mitochondrial morphology and function under hypoxia in the shoulder tendon tissue from surgically-induced tenotomy-RCI rat model and cultured swine tenocytes. The tendon tissue was collected post-injury on 3–5 (Group-A), 10–12 (Group-B), and 22–24 (Group-C), days and the corresponding contralateral tendons were used as control for each group. There was higher protein expression of citrate synthase (P < 0.0001) [10.22 MFI (mean fluorescent intensity)] and complex-1 (P = 0.0008) (7.86 MFI) in Group-A and Group-B that decreased in Group-C [(P = 0.0201) (5.78 MFI and (P = 0.7915) (2.32 MFI), respectively] compared to control tendons. The ratio of BAX:Bcl2 (Bcl2 associated x protein:B cell lymphoma 2) in RCI tendons increased by 50.5% (Group-A) and 68.4% (Group-B) and decreased by 25.8% (Group-C) compared to normoxic controls. Hypoxia increased β-tubulin expression (P = 0067) and reduced PGC1-α (P = 0412) expression in the isolated swine tenocytes with no effect on the protein expression of Complex-1 (P = 7409) and citrate synthase (P = 0.3290). Also, the hypoxic tenocytes exhibited about 4-fold increase in mitochondrial superoxide (P < 0.0001), altered morphology and mitochondrial pore integrity, and increase in mitochondrial density compared to normoxic controls. These findings suggest the critical role of mitochondria in the RCI healing response.

show abstract

Apoptosis and rotator cuff tears: scientific evidence from basic science to clinical findings

Abstract: Further studies are needed to produce clear guidelines to determine how to balance the apoptosis process to reduce the failed healing response found in non-traumatic RC tears.

Cited by 21 publications

References 42 publications

Nuclear lamin A in rotator cuff tear margin tenocytes: an antiapoptotic and cell mechanostat factor

Nuclear lamin A in rotator cuff tear margin tenocytes: an antiapoptotic and cell mechanostat factor

Gene Expression Patterns Analysis in the Supraspinatus Muscle after a Rotator Cuff Tear in a Mouse Model

Amplification of Mitochondrial Activity in the Healing Response Following Rotator Cuff Tendon Injury

Contact Info

Product

Resources

About