Advanced quantitative proteomics to evaluate molecular effects of low-molecular-weight hyaluronic acid in human dermal fibroblasts

Radrezza, Silvia; Baron, Giovanna; Nukala, Sarath Babu; Depta, Gabriele; Aldini, Giancarlo; D’Amato, Alfonsina

doi:10.1016/j.jpba.2020.113199

Cited by 14 publications

(24 citation statements)

References 20 publications

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“…Label-free proteomics analyses conducted in our previous study showed a significant alteration of human dermal fibroblasts protein profile induced by LMW-HA, mainly at 0.50% of concentration ( Table 1 A) [ 10 ]. Indeed, proteins representing pathways such as cell proliferation and growth, extracellular matrix reorganization, proteoglycans biosynthesis, mitochondrial activity, cell adhesion, or wound healing were significantly upregulated.…”

Section: Resultsmentioning

confidence: 99%

“…Despite its increasing use, the molecular action of LMW-HA is still less known. In our previous work, we showed a significant impact of 20–50 kDa LWM-HA on the proteome profile of normal human dermal fibroblasts, especially at the highest concentration (0.50% LMW-HA) [ 10 ]. Here, applying high-resolution mass spectrometry and network analyses, we focused our attention on lipidome profile changes of human dermal fibroblasts (HDF) induced by the same treatment conditions (0.125, 0.25, and 0.50% LMW-HA, 24 h).…”

Section: Introductionmentioning

confidence: 99%

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Integratomics of Human Dermal Fibroblasts Treated with Low Molecular Weight Hyaluronic Acid

et al. 2021

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Hyaluronic acid (HA) is a glycosaminoglycan very common in commercial products from pharmaceuticals to cosmetics due to its widespread distribution in humans and its diversified physico-chemical proprieties. Despite its extended use and preliminary evidence showing even also opposite activities to the native form, the precise cellular effects of HA at low-molecular-weight (LWM-HA) are currently unclear. The ‘omics sciences currently in development offer a new and combined perspective on the cellular and organismal environment. This work aims to integrate lipidomics analyses to our previous quantitative proteomics one for a multi-omics vision of intra- and extra-cellular impact of different concentrations (0.125, 0.25, and 0.50%) of LMW-HA (20–50 kDa) on normal human dermal fibroblasts by LC-high resolution mass spectrometry (LC-HRMS). Untargeted lipidomics allowed us to identify 903 unique lipids mostly represented by triacylglycerols, ceramides, and phosphatidylcholines. According to proteomics analyses, LMW-HA 0.50% was the most effective concentration also in the lipidome rearrangement especially stimulating the synthesis of ceramides involved in skin hydration and reparation, cell signaling, and energy balance. Finally, integrative analyses showed 25 nodes covering several intra- and extra-cellular functions. The more complete comprehension of intra- and extra-cellular effects of LMW-HA here pointed out will be useful to further exploit its features and improve current formulations even though further studies on lipids biosynthesis and degradation are necessary.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integratomics of Human Dermal Fibroblasts Treated with Low Molecular Weight Hyaluronic Acid

et al. 2021

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“…LMW-HA promotes a proinflammatory response, inhibits fibrocyte differentiation, enhances intracellular activity and extracellular matrix reorganization, and increases proteoglycans and collagen biosynthesis. 14,24,25 Also, LMW-HA enhances acid phosphatase activity and acid phosphatase-positive multinucleated cell formation, whereas HMW-HA did not affect osteoclast differentiation. LMW-HA enhances pit formation in the process of osteogenesis, whereas HMW-HA does not.…”

Section: Discussionmentioning

confidence: 97%

“…It binds to water, lubricates mobile parts of the body, and reduces scar formation through exerting antifibrotic and anti-inflammatory effects. 14,15 Research studies showed that, if injected around the shoulder joint, HA serves as a lubricant, prevents degeneration of the articular cartilage, and relieves inflammation. 16,17 The medication has been used successfully for subacromial impingement syndrome without a complete tear of the rotator cuff.…”

Section: Introductionmentioning

confidence: 99%

High- Versus Low-Molecular-Weight Hyaluronic Acid for the Treatment of Rotator Cuff Tendinopathy: A Triple-Blind Randomized Comparative Trial

et al. 2021

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Background Shoulder pain most commonly originates from the tendon structures of the rotator cuff. Objective We compared the clinical effects of high- versus low-molecular-weight (LMW) hyaluronic acid for the management of rotator cuff tendinopathy. Methods We carried out a parallel, triple-blind, randomized comparative trial at a teaching hospital. In total, 56 patients aged 16 to 70 years with rotator cuff tendinopathy were randomly allocated to 2 groups. We administered a single shoulder injection of either 1 mL of 1% high- (>2000 kDa) or 1 mL of 1% LMW hyaluronate (500-700 kDa) to the corresponding groups. The primary outcome was the intensity of shoulder pain. The secondary outcomes were range of motion and disability of the shoulder, and quality of life. We performed the measurements at baseline and at 1, 4, and 12 weeks postintervention. The pain measurements were repeated at the sixth month postintervention. Results Comparisons of baseline versus 3 months showed that both interventions were beneficial in the management of the tendinopathy (all P values <0.05). However, between-group analyses did not indicate any clinically significant difference between the 2 medications. The pain, induration ( P = 0.007), and inflammation at the site of the injection were less prominent for LMW hyaluronate. Conclusion and Relevance Both medications are effective for the treatment of tendinopathy. The benefits last at least for 3 months, and pain alleviation lasts partially for 6 months. The shoulder injection of LMW hyaluronate is more tolerable to the patient. Therefore, we recommend LMW hyaluronate as the first choice for the management of rotator cuff tendinopathy.

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“…This was achieved through a DDA screening using nano LC‐Q‐Orbitrap‐MS together with network protein analysis to identify and quantify the proteome's changes. Overall, 2328 proteins were identified of which 39 altered significantly in 0.125% LWM‐HA, 149 in 0.25% LWM‐HA, and 496 in 0.50% LWM‐HA 65 . This work has filled a gap in drug understanding and can be useful for the improvement of existing formulations and personalized treatments.…”

Section: Post‐approval Analyses and Hrms Quantificationmentioning

confidence: 94%

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

Géhin

Holman

2021

Analytical Science Advances

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Continuous improvements in mass spectrometry (MS) have resulted in the widespread availability and adoption of high‐resolution mass spectrometry (HRMS) across laboratories worldwide. The capabilities and the associated advantages of HRMS make it an invaluable analytical tool for analyte characterization, screening, and quantification methodologies for a wide scope of applications across pharmaceutical development. These applications include drug discovery, product characterizations of both small molecules and novel drug modalities, in vitro and in vivo metabolism studies, post‐approval quality control, and pharmacovigilance. This review gives an overview of the current capabilities of HRMS and its pharmaceutical applications in 2020, and provides a perspective on the future of HRMS within the pharmaceutical industry.

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Advanced quantitative proteomics to evaluate molecular effects of low-molecular-weight hyaluronic acid in human dermal fibroblasts

Cited by 14 publications

References 20 publications

Integratomics of Human Dermal Fibroblasts Treated with Low Molecular Weight Hyaluronic Acid

Integratomics of Human Dermal Fibroblasts Treated with Low Molecular Weight Hyaluronic Acid

High- Versus Low-Molecular-Weight Hyaluronic Acid for the Treatment of Rotator Cuff Tendinopathy: A Triple-Blind Randomized Comparative Trial

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

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