Reduced telomere length is associated with fibrotic joint disease suggesting that impaired telomere repair contributes to joint fibrosis

Kalson, Nicholas S.; Brock, Tim M; Mangino, Massimo; Fabiane, Stella M.; Mann, Derek A.; Borthwick, Lee A.; Deehan, David J.; Williams, Frances

doi:10.1371/journal.pone.0190120

Cited by 7 publications

(3 citation statements)

References 21 publications

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“…Kalson et al. [ 28 ] studied the mean leukocyte telomere length (LTL) in a cohort study which checked for the correlation between joint fibrosis and telomeres. The authors concluded that in patients with adhesive capsulitis an altered telomere length was present and it could lead to severe tissue fibrosis.…”

Section: Discussionmentioning

confidence: 99%

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis: an immunohistochemical study on lamin A/C expression

Candela,

Peruzzi,

Leopizzi

et al. 2024

J Orthop Traumatol

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Background The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamina. Lamins have been associated with important cellular functions: DNA replication, chromatin organization, differentiation of the cell, apoptosis and in maintenance of nuclear structure. Little is known regarding the etiopathogenesis of adhesive capsulitis (AC); recently, a dysregulating fibrotic response starting from a subpopulation has been described within the fibroblast compartment, which suddenly turns on an activated phenotype. Considering the key role of A-type lamins in the regulation of cellular stability and function, our aim was to compare the lamin A/C expression between patients with AC and healthy controls. Materials and methods A case–control study was performed between January 2020 and December 2021. Tissue samples excised from the rotator interval were analysed for lamin A/C expression by immunohistochemistry. Patients with AC were arbitrarily distinguished according to the severity of shoulder flexion limitation: ≥ 90° and < 90°. Controls were represented by samples obtained by normal rotator interval excised from patients submitted to shoulder surgery. The intensity of staining was graded, and an H-score was assigned. Statistical analysis was performed (Chi-square analysis; significance was set at alpha = 0.05). Results We enrolled 26 patients [12 male and 14 female, mean age (SD): 52.3 (6.08)] and 15 controls [6 male and 9 female, mean age (SD): 57.1 (5.3)]. The expression of lamin A/C was found to be significantly lower in the fibroblasts of patients with adhesive capsulitis when compared with controls (intensity of staining: p: 0.005; H-score: 0.034); no differences were found regarding the synoviocytes (p: > 0.05). Considering only patients with AC, lamin A/C intensity staining was found to be significantly higher in samples where acute inflammatory infiltrate was detected (p: 0.004). No significant changes in levels of lamin A/C expression were documented between the mild and severe adhesive capsulitis severity groups. Conclusions Our study demonstrated that the activity of lamin A/C in maintaining nuclear structural integrity and cell viability is decreased in patients with adhesive capsulitis. The phase of the pathogenetic process (freezing and early frozen) is the key factor for cell functionality. On the contrary, the clinical severity of adhesive capsulitis plays a marginal role in nuclear stability. Level of evidence III.

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Section: Discussionmentioning

confidence: 99%

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis: an immunohistochemical study on lamin A/C expression

Candela,

Peruzzi,

Leopizzi

et al. 2024

J Orthop Traumatol

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“…A short telomere length is suggested to be associated with, or predict, many common aging diseases, including various geriatric diseases, such as cancer, dementia, and osteoporosis [1,4]. Furthermore, in a prospective study by Goglin et al [5], an increase in telomere length resulted in a lower mortality rate, while a decrease in telomere length resulted in a higher mortality rate.…”

Section: Introductionmentioning

confidence: 99%

Does Exercise Affect Telomere Length? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Song¹,

Lee

Kim³

2022

Medicina

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Background and objectives: Telomere length is an indicator of biological aging, and it shortens during cell division. A short telomere length is associated with various age-related diseases and mortality. It is suggested that physical activity has a positive effect on the rate of telomere length shortening. Materials and Methods: Related studies, published in electronic databases, were searched with keywords, including exercise, telomere length, and randomized controlled trial. The data were weighted and pooled through a fixed-effect model. Results: Of the total 49 studies searched, 7 studies with 939 participants were considered suitable, and were analyzed qualitatively and quantitatively. Exercise is beneficial to telomere length. Aerobic exercise was effective as the type of exercise (MD, −0.03; 95% CI, −0.04 to −0.01). In addition, exercise for more than 6 months, with a change in lifestyle, is beneficial for telomere length (MD, −0.02; 95% CI, −0.04 to −0.01). Conclusions: The type and duration of exercise for positive improvement in telomere length is aerobic exercise for more than 6 months.

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“…Approximated five percent of patients suffer stiffness as a significant complication after their TKA [ 6 ], and some require manipulation under anaesthesia [ 22 ] or revision surgery because of persistent stiffness [ 18 ]. Stiffness after knee arthroplasty may have a genetic component and epidemiological studies have found chromosomal changes in those reporting such symptoms [ 14 ], with an increased understanding of the biological basis for such a host response [ 16 ]. This is leading to a greater awareness that stiffness is potentially avoidable both from a mechanical and biological perspective [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Increased symptoms of stiffness 1 year after total knee arthroplasty are associated with a worse functional outcome and lower rate of patient satisfaction

Clement

Bardgett

Weir

et al. 2018

Knee Surg Sports Traumatol Arthrosc

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Purpose Symptoms of stiffness after total knee arthroplasty (TKA) cause significant morbidity, but there is limited data to facilitate identification of those most at risk after surgery. Stratifying risk can aid earlier directed treatment options. Methods A retrospective cohort consisting of 2589 patients undergoing a primary TKA was identified from an established arthroplasty database. Patient demographics, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and short form (SF) 12 scores were collected pre-operatively and 1 year post-operatively. In addition, patient satisfaction was assessed for 1 year. Patients with a worse WOMAC stiffness score in 1 year were defined as the "increased" stiffness group and the other cohort as the non-stiffness group. Results At 1 year after surgery 129 (5%) patients had a significant increase in their stiffness symptoms (20%, 95% confidence interval (CI) 17.9-22.0, p < 0.001), and had significantly (all p < 0.001) less of an improvement in their pain, function and total WOMAC scores, and SF-12 scores compared to the non-stiffness group (n = 2460). Patient satisfaction was significantly lower (odds ratio (OR) 0.178, CI 0.121 to 0.262, p < 0.001) for the increased stiffness group. Logistic regression analysis identified male gender (OR 1.66, p = 0.02), lung disease (OR 2.06, p = 0.002), diabetes (OR 1.82, p = 0.02), back pain (OR 1.81, p = 0.005), and a pre-operative stiffness score of 44 or more (OR 5.79, p < 0.001) were significantly predictive of increased stiffness. Conclusion Patients with increased symptoms of stiffness after TKA have a worse functional outcome and a lower rate of patient satisfaction, and patients at risk of being in this group should be informed pre-operatively. Level of evidence Retrospective prognostic study, Level III.

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Reduced telomere length is associated with fibrotic joint disease suggesting that impaired telomere repair contributes to joint fibrosis

Cited by 7 publications

References 21 publications

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis: an immunohistochemical study on lamin A/C expression

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis: an immunohistochemical study on lamin A/C expression

Does Exercise Affect Telomere Length? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Increased symptoms of stiffness 1 year after total knee arthroplasty are associated with a worse functional outcome and lower rate of patient satisfaction

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