The Impact of Hyaluronic Acid on Tendon Physiology and Its Clinical Application in Tendinopathies

Oliva, Francesco; Marsilio, Emanuela; Asparago, Giovanni; Frizziero, Antonio; Berardi, Anna C.; Maffulli, Nicola

doi:10.3390/cells10113081

Cited by 42 publications

(32 citation statements)

References 95 publications

(114 reference statements)

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“…Further policies are pharmacologically oriented [ 28 ], such as using biolubricants in order to enhance the gliding capacity [ 29 ]. Among natural lubricants, hyaluronic acid (HA) is highly promising [ 30 , 31 ] because it occurs as the main lubricating agent in the natural synovial fluid [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro

Miescher

Wolint

Opelz

et al. 2022

IJMS

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(1) Background: Surgical tendon repair often leads to adhesion formation, leading to joint stiffness and a reduced range of motion. Tubular implants set around sutured tendons might help to reduce peritendinous adhesions. The lubricant hyaluronic acid (HA) is a viable option for optimizing such tubes with the goal of further enhancing the anti-adhesive effect. As the implant degrades over time and diffusion is presumed, the impact of HA on tendon cells is important to know. (2) Methods: A culture medium of rabbit Achilles tenocytes was supplemented with high-molecular-weight (HMW) HA and the growth curves of the cells were assessed. Additionally, after 3, 7 and 14 days, the gene expression of several markers was analyzed for matrix assembly, tendon differentiation, fibrosis, proliferation, matrix remodeling, pro-inflammation and resolution. (3) Results: The addition of HA decreased matrix marker genes, downregulated the fibrosis marker α-SMA for a short time and slightly increased the matrix-remodeling gene MMP-2. Of the pro-inflammatory marker genes, only IL-6 was significantly upregulated. IL-6 has to be kept in check, although IL-6 is also needed for a proper initial inflammation and efficient resolution. (4) Conclusions: The observed effects in vitro support the intended anti-adhesion effect and therefore, the use of HMW HA is promising as a biodegradable implant for tendon repair.

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Section: Discussionmentioning

confidence: 99%

Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro

Miescher

Wolint

Opelz

et al. 2022

IJMS

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“…The etiology of ATRs is multifactorial, and several intrinsic and extrinsic risk factors can be identified. While age, sex, and systemic conditions are non-modifiable predictors of rupture, BMI, use of different types of drugs, and sport involvement represent modifiable risk factors [12][13][14]. Metabolic diseases, such as diabetes mellitus, hypercholesterolemia, thyroid disorders, and obesity, impair tendon health, leading to Achilles tendinopathy and predisposing one to ATR [15].…”

Section: Introductionmentioning

confidence: 99%

Achilles Tendon Rupture and Dysmetabolic Diseases: A Multicentric, Epidemiologic Study

Oliva

Marsilio

Asparago

et al. 2022

JCM

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Introduction: Achilles tendon ruptures are common. Metabolic disorders, such as diabetes mellitus, hypercholesterolemia, thyroid disorders, and obesity, impair tendons health, leading to Achilles tendinopathy and likely predisposing patients to Achilles tendon ruptures. Materials and methods: Patients who visited the Orthopedic Outpatient Clinics and the Accident and Emergency Departments of five different hospitals in Italy were recruited. Through telephone interviews, we administered a questionnaire to all the patients who had undergone surgical ATR repair, evaluating their past medical history, sport- and work-related activities, drug use, and post-operative rehabilitation outcomes. Results: “Return to work activities/sport” was negatively predicted by the presence of a metabolic disorder (β = −0.451; OR = 0.637) and ‘open’ surgery technique (β = −0.389; OR = 0.678). “Medical complications” were significantly predicted by metabolic disorders (β = 0.600 (0.198); OR = 1.822) and was negatively related to ‘mini-invasive’ surgery (i.e., not ‘open’ nor ‘percutaneous’) (β = −0.621; OR = 0.537). “Immediate weightbearing” and “immediate walking without assistance” were negatively predicted by ‘open’ technique (β = −0.691; OR = 0.501 and β = −0.359 (0.174; OR = 0.698)). Conclusions: Metabolic conditions can strongly affect post-operative outcomes following surgical repair of acute Achilles tendon tears.

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“…It has been widely demonstrated that the accumulation of reactive oxygen species (ROS) stimulates the intracellular antioxidant system, which is tightly regulated by Nrf2 (nuclear factor erythroid 2 (NF-E2)-related factor 2) [ 5 ], and that a functional tendon-repair failure might be strongly associated with the activation of the Nrf2 pathway [ 6 ]. Recently, hyaluronic acid (HA) has been suggested for the clinical management of tendinopathies [ 7 , 8 ]. Our previous studies demonstrated that different HA preparations, depending on their molecular weight, counteracted apoptosis under H 2 O 2 -induced OS [ 9 ], enhanced cell recovery from H 2 O 2 exposure in terms of decreased cytotoxicity and reduced Nrf2 expression, and increased the expression of the HA receptor CD44 [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…HA, as one of the fundamental components of cartilage and tendons, contributes to their viscoelastic properties in vivo [ 8 , 11 , 12 ]. However, HA efficacy in the management of RCT is still debated and a comprehensive description of the underlying molecular mechanisms involved is still lacking [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid Alleviates Oxidative Stress and Apoptosis in Human Tenocytes via Caspase 3 and 7

Gallorini

Passeri

Cataldi

et al. 2022

IJMS

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Rotator cuff tendinopathy (RCT) is the primary reason for shoulder surgery and its clinical management is still challenging. Hyaluronic acid (HA) has been shown to have anti-inflammatory effects in vitro and in vivo under RCT conditions, characterized by an exaggerated oxidative stress (OS). However, molecular mechanisms underlying HA-related effects are still partially disclosed. With these aims, a cell model of RCT was established by exposing primary human tenocytes to H2O2 for up to 72 h. Four different HAs by molecular weight were administered to measure nitric oxide (NO) and OS, apoptosis, and collagen 1 expression. In parallel, the well-known antioxidant ascorbic acid was administered for comparison. The present study highlights that HAs characterized by a low molecular weight are able to counteract the H2O2-induced OS by decreasing the percentage of apoptotic cells and reversing the activation of caspase 3 and 7. Likewise, NO intracellular levels are comparable to the ones of controls. In parallel, collagen 1 expression was ameliorated by HAs characterized by higher molecular weights compared to AA. These findings confirm that HA plays an antioxidant role comparable to AA depending on the molecular weight, and highlight the molecular mechanisms underlying the HA anti-apoptotic effects.

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The Impact of Hyaluronic Acid on Tendon Physiology and Its Clinical Application in Tendinopathies

Cited by 42 publications

References 95 publications

Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro

Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro

Achilles Tendon Rupture and Dysmetabolic Diseases: A Multicentric, Epidemiologic Study

Hyaluronic Acid Alleviates Oxidative Stress and Apoptosis in Human Tenocytes via Caspase 3 and 7

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