Table 4 Characteristics of the included studies according to the PICO(S) scheme
Author | Population | Intervention | Localization | Outcome |
|---|---|---|---|---|
Feng et al. [47] | 6 healthy male subjects, 31 ± 4 years of age | An experimental group was treated with miR-6924-5p and compared with a comparison group (no treatment) for various osteoclastogenesis markers | Whole blood (monocytes) | Monocytes treated with the miR-6924-5p had significantly downregulated osteoclastogenesis markers compared to the control group |
Sun et al. [53] | 10 male and 16 female patients, 60 ± 7 years of age | An in vitro model was used to investigate the function of HMGA2 in human tendon stem cells treated with H2O2 | Supraspinatus tendon | H2O2 leads to increased Nudt21 expression and thus increased let-7 production in tendon stem cells |
Ge et al. [42] | 2 male and 8 female subjects 5 patients 47–71 years of age and 5 subjects 44–66 years of age | Profiling of lncRNAs, mRNAs and miRNAs involved in rotator cuff tendinopathy in comparison with healthy tendons | Supraspinatus tendon | The analysis identified 35 miRNAs whose expression was significantly altered in tendinopathies compared with healthy tendons |
Plachel et al. [41] | Investigation 1: 2 male and 3 female healthy subjects, 58.1 ± 6 years of age, 3 male and 2 female patients, 57.0 ± 5.9 years of age, 2 male and 2 female patients, 60.1 ± 8.4 years of age Investigation 2: 1 male and 3 female patients 62.4 ± 10.1 years of age, 5 male and 2 female patients, 64.8 ± 7.9 years of age,8 healthy male subjects, 29.8 ± 8.1 years of age | miRNA profiles were compared between healthy subjects as well as patients with chronic tendinopathies and patients with degenerative rotator cuff tears | Venous blood, Subscapularis tendon, Supraspinatus tendon | Several miRNAs were found to be significantly dysregulated when comparing the different groups |
Xiao et al. [57] | 2 healthy subjects, sex unclear, mean age 24.5 years | Human tenocytes were treated with miR mimics and antagomirs of miR-30d, 26a, and 29a. Subsequently, gene expression was evaluated for scleraxis, collagen 1 alpha 1, collagen 3 alpha 1, IL-1β, IL-6, BMP2, BMP12, and osteocalcin | Patellar tendon | miR-29a mimics and mir-29a-antagomir resulted in a significant reduction of BMP2 in human tenocytes. In addition, there was a significant reduction of BMP12 by miR-29a mimics |
Thankam et al. [55] | 8 patients, sex and age unknown | Tendon samples were compared between one group with tendon injury and fat infiltration vs. one group with tendon injury but without fat infiltration to find out which miRNAs are different | Biceps tendon | 13 highly significant miRNAs and 216 target genes were identified |
Hall et al. [43] | 5 male patients, 44–65 years of age | One tendinopathic supraspinatus tendon and one healthy subscapularis tendon from each of 5 patients were biopsied, and the expression of miRNAs was compared | Subscapularis tendon, Supraspinatus tendon | Twenty-one miRNAs were identified that showed significantly altered expression between the healthy and tendinopathic tendons |
Ge et al. [48] | Patients, n unknown, sex unknown, age 40.4 ± 10.3 years of age and patients, n unknown, sex unknown, 36.3 ± 11.5 years of age | Investigation of the role of miR-148a-3p in the development of angiogenesis in tendinopathies | Supraspinatus tendon | The miR-148a-3p is significantly upregulated in tendinopathic tendons. miR-148a-3p upregulates the expression of thrombospondin-4 and promotes angiogenesis by inhibiting Krüppel-like factor 6 |
Thankam et al. [40] | 8 patients, sex and age unknown | Investigation of miRNAs associated with the JAK2/STAT3 pathway. In addition, target genes associated with glenohumeral arthritis and rotator cuff tears were identified | Biceps tendon | 235 miRNAs were identified whose expression was significantly altered between group 1 and group 2. In addition, 284 target genes related to the JAK/STAT3 pathway were identified |
Han et al. [49] | Young healthy subjects, n unknown, sex unknown, 25 ± 8 years of age, old subjects with tendon degeneration, n unknown, sex unknown, age 65 ± 10 years | It was investigated whether the senescence marker p16 affects age-related tenogenic differentiation in tendon stem/progenitor cells (TSPCs). For this purpose, young and old TSPCs were compared. In addition, a mir-217 mimic or a miR-217 inhibitor was added to the TSPCs and the effect was examined | Achilles tendon | The miR-217 was significantly upregulated in old tendon stem cells, furthermore, an increase in p16 was detected with a parallel decrease in type 1 collagen. Downregulation of miR-217 reversed the inhibitory effect of p16 on tenogenic differentiation of old TSPCs |
Leal et al. [44] | 19 male, 21 female patients, age 56.2 ± 11.1 years, 5 male and 6 female subjects, age 57.5 ± 14.1 years without tendon injury | Comparison between injured and healthy tendons, regarding mRNA expression, DNA methylation status, the MMP and TIMP genes, and miR-29 family expression | Supraspinatus tendon | miR-29a-3p, miR-29b-3p, miR-29b-5p correlated (inversely) significantly with MMP2, MMP9, and MMP 14; in addition, miR-29a-3p and miR-29b-5p correlated significantly with MMP1. No differences in miRNA-29 family expression between injured and healthy tendons |
Brown et al. [46] | 130 healthy subjects, sex and age unknown, 112 patients sex and age unknown | Comparison between patients with chronic Achilles tendinopathy and healthy control group regarding 8 different genes, including MIR608, which encodes mir-608 | Saliva | Individuals with MIR 608 genotype encoding miR-608 had significantly lower risk of Achilles tendon injury |
Lu et al. [50] | 2 healthy male patients, 38 and 43 years of age | It was investigated whether long non-coding RNA (lncRNA) H19 affects tenogenesis of human tendon stem cells. In addition, the effect of miR-29b-3p-mimics and anti-miR-29b-3p on H19 was investigated | Bone marrow, Hamstring tendon | The lncRNA H19 increases TGF-ß expression and promotes tenogenic differentiation by inhibiting miR-29b-3p. miR-29b-3p inhibited the expression of TGF-ß and type I collagen |
Thankam et al. [54] | 8 patients, sex and age unknown | Microarray analysis to determine which miRNAs play a critical role in tendon tissue inflammation | Biceps tendon | 7 miRNAs were found to have a significant change in expression pattern in inflamed tendons |
Wang et al. [56] | Unclear | The effect of miR-124 on collagen formation in TDSCs was investigated | Unclear | miR-124 controls collagen formation in TGF-ß1-induced differentiation of tendon stem cells by significantly inhibiting egr1 expression |
Hu et al. [60] | 3 male patients, mean age 26.5Â years | This study aimed to investigate the osteogenic effects induced by extracorporeal shock waves on TDSCs among others, and their underlying mechanisms | Patellar tendon | miR-138 was significantly downregulated in TDSCs by extracorporeal shock waves, resulting in increased osteogenic differentiation |
Chen et al. [59] | 2 subjects, sex unknown 28 and 31Â years | To investigate the role of PIN-1 in the aging of TSPCs. In addition, the role of miR-140-5p in association with PIN-1 was studied | Achilles tendon | miR-140-5p has a significant effect on PIN-1 expression, which is associated with senescence in tendon stem cells |
Millar et al. [51] | 17 patients, sex unknown, mean age 54Â years, 10 healthy subjects, sex unknown mean age 35Â years | The role of IL-33 in association with miR-29a in early tendinopathies was analyzed | Supraspinatus tendon, Subscapularis tendon | Addition of IL33 significantly downregulated miR-29a. Downregulation of miR-29a significantly increased collagen-3 production. Addition of a miR-29a mimic significantly decreased collagen-3 production |
Cai et al. [58] | 23 healthy subjects, sex and age unknown, 23 patients, sex and age unknown | Tendinopathic samples were compared with healthy control samples, and their miRNA expression was investigated via microrray analysis | Unclear | During the analysis, 15 miRNAs were located that showed a significantly different expression pattern |
Peffers et al. [52] | 2 male and 3 female patients 69.4 ± 7.3 years of age, 4 male patients 19 ± 5.8 years of age, 4 young subjects sex unknown, 16.7 ± 2.8 years of age 4 old subjects, sex unknown 73.2 ± 6.5 years of age | Gene expression analysis was performed, and the results found were compared between old and young individuals. Subsequent validation by control group | Achilles tendon | A total of 325 elements were found including one miRNA, miR-1245A, whose expression differed significantly between young vs. old individuals |
Poulsen et al. [61] | Unclear | Tendon cells were cultured in high or low glucose concentration and the miRNAs which had a significant changed expression were determined | Hamstring tendon | High glucose (oxidative stress) leads to significant upregulation of miR-28-5p which results in apoptosis of tenocytes |
Abrahams et al. [45] | 342 asymptomatic subjects, 160 patients with chronic Achilles tendon tendinopathy, sex and age unclear | This study aimed to compare the polymorphism of individuals with Achilles tendinopathy with a healthy control group | Unclear | The MIR608 gene encoding miR-608 may be associated with Achilles tendon tendinopathies |