Therapeutic potential of microRNA in tendon injuries

Giordano, Lorenzo; Porta, Giovanna Della; Peretti, G.M.; Maffulli, Nicola

doi:10.1093/bmb/ldaa002

Cited by 122 publications

(94 citation statements)

References 73 publications

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“…The resident tenocytes finely regulate the anabolic and catabolic processes taking place in the extracellular matrix, and they mediate tendon repair by a complex modulation of tendon homeostasis. Recently, specific miRNAs have been described for tendon matrix healing and regeneration [20].…”

Section: Tendon Propertiesmentioning

confidence: 99%

In Vitro Innovation of Tendon Tissue Engineering Strategies

Citeroni

Ciardulli

Russo

et al. 2020

IJMS

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Tendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process.

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Section: Tendon Propertiesmentioning

confidence: 99%

In Vitro Innovation of Tendon Tissue Engineering Strategies

Citeroni

Ciardulli

Russo

et al. 2020

IJMS

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“…Given the huge gap of knowledge regarding the biology of tendon healing and the sequence of events and biomolecules involved, a diversity of growth factors are used for tendon research [2,23]. Among these, GDF family members, and more precisely, Growth Differentiation Factor 5 (GDF- 5), have been used successfully to drive tenogenic differentiation. GDF-5 belongs to the TGF-β superfamily, and it is highly expressed in mesenchymal condensations during skeleton development.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical manifestation itself is the result of a long-term interplay of inflammatory and failed healing response changes [ 3 ]. The management of tendon injuries is challenging, given their limited healing capability, and propensity for a failed healing response [ 4 , 5 ]. Anti-inflammatory drugs are frequently used, but they may actually hinder recovery [ 6 ], while in clinical practice, tissue grafts or prostheses are used for severe injuries [ 7 , 8 ], and cell therapies are proposed for future application [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells

Ciardulli

Marino

Lamparelli

et al. 2020

IJMS

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Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.

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“…Using this pathway, miRNAs play important roles in homeostatic processes including cell proliferation, differentiation, and cell death [ 5 ]. miRNAs are vital post-transcriptional modulators of gene expression that govern the osteoblast-mediated bone formation, thus involving in OP, osteoarthritis, and other bone-related disorders [ 6 – 8 ]. For instance, advanced PCR arrays adopted by a previous research team found that circulating hsa-miR-122-5p and hsa-miR-4516 exhibited potential diagnostic potentials for OP [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

et al. 2020

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Background Osteoporosis (OP) has the characteristics of the decline in bone mineral density and worsening of bone quality, contributing to a higher risk of fractures. Some microRNAs (miRNAs) have been validated as possible mediators of osteoblast differentiation. We herein aimed to clarify whether miR-497-5p regulates the differentiation of osteoblasts in MC3T3-E1 cells. Methods The expression of miR-497-5p in OP patients and controls was measured by RT-qPCR, and its expression changes during osteoblast differentiation were determined as well. The effects of miR-497-5p on the differentiation of MC3T3-E1 cells were studied using MTT, ALR staining, and ARS staining. The target gene of miR-497-5p was predicted by TargetScan, and the effects of its target gene on differentiation and the pathway involved were investigated. Results miR-497-5p expressed poorly in OP patients, and its expression was upregulated during MC3T3-E1 cell differentiation. Overexpression of miR-497-5p promoted mineralized nodule formation and the expression of RUNX2 and OCN. miR-497-5p targeted high mobility group AT-Hook 2 (HMGA2), while the upregulation of HMGA2 inhibited osteogenesis induced by miR-497-5p mimic. miR-497-5p significantly impaired the c-Jun NH2-terminal kinase (JNK) pathway, whereas HMGA2 activated this pathway. Activation of the JNK pathway inhibited the stimulative role of miR-497-5p mimic in osteogenesis. Conclusions miR-497-5p inhibits the development of OP by promoting osteogenesis via targeting HMGA2.

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Therapeutic potential of microRNA in tendon injuries

Cited by 122 publications

References 73 publications

In Vitro Innovation of Tendon Tissue Engineering Strategies

In Vitro Innovation of Tendon Tissue Engineering Strategies

Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

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