Could Hyaluronic Acid Be Considered as a Senomorphic Agent in Knee Osteoarthritis? A Systematic Review

Abstract

Background: Knee osteoarthritis (KOA) is one of the most common causes of disability in elderly patients and tends to be a major burden on social and health care spending. Despite its severe socioeconomic impact, KOA remains, to date, an incurable disease. Due to its proper characteristics, KOA represents a favorable disease model for experimenting with senotherapeutics, a group of treatments that counteract the development of age-related disorders and chronic diseases. In recent years, the use of intra-articular hyaluronic acid (IAHA) in the treatment of diseases related to the wear and tear of the articular cartilage has been gaining popularity. Given its ability in joint lubrification, shock absorption, and cell signaling, our aim is to investigate, through the existing scientific literature, its potential role as a senomorphic agent, emphasizing its crucial function in KOA patients. Indeed, senomorphics are a particular group of senotherapeutics capable of modulating the functions and morphology of senescent cells to those of young cells or delaying the progression of young cells to senescent cells in tissues. Methods: A search in the scientific literature (PubMed, Cochrane Library, and Google Scholar) was carried out from 2019 to 2023, thus the last 5 years. Results: One hundred thirty-eight articles were found concerning the role of hyaluronic acid injections in KOA patients. In these studies, its therapeutic efficacy, its anti-inflammatory properties, and its low risk of side effects emerged. Conclusion: IAHA injections are a valuable treatment option for KOA while they can provide pain relief, improve joint function, and slow the progression of joint degeneration. The inhibitory effect of HA on MMP13 and its action as a senomorphic agent suggests that it may have additional benefits beyond its lubricating and shock-absorbing properties. In order to clarify its mechanisms of action and to optimize its clinical use, further studies are definitely needed.

Clinical and Biochemical Implications of Hyaluronic Acid in Musculoskeletal Rehabilitation: A Comprehensive Review

“…This review article primarily provided an in-depth exploration of HA's functions and properties. It is evident that these properties collectively establish HA as an exceptionally effective therapeutic compound for a wide range of medical conditions, especially those related to musculoskeletal diseases, and as a senomorphic agent [123]. Consequently, several HA-based products have been developed and are readily accessible in the market.…”

The Synergistic Effects of Hyaluronic Acid and Platelet-Rich Plasma for Patellar Chondropathy

“…Additional benefits of HA go beyond the traditional lubricating and shock-absorbing properties. According to a recent systematic review [107], HA also displays senomorphic properties. Senomorphics refers to a group of therapeutic agents capable of manipulating the function and morphology of senescent cells to a similar profile seen in young cells or at least delaying the progression of senescence [107].…”

“…According to a recent systematic review [107], HA also displays senomorphic properties. Senomorphics refers to a group of therapeutic agents capable of manipulating the function and morphology of senescent cells to a similar profile seen in young cells or at least delaying the progression of senescence [107]. In other words, HA can control the production of senescence-associated secretory phenotype (SASP) and other substances, such as cytokines and MMPs, which are involved in cellular damage due to aging [107].…”

“…Senomorphics refers to a group of therapeutic agents capable of manipulating the function and morphology of senescent cells to a similar profile seen in young cells or at least delaying the progression of senescence [107]. In other words, HA can control the production of senescence-associated secretory phenotype (SASP) and other substances, such as cytokines and MMPs, which are involved in cellular damage due to aging [107]. HA's senotherapeutic potential is mainly attributed to the upregulation of sirtuin 1 and its reductive effect on oxidative stress [108], marked by a particular reduction in MMP 13, specifically [109].…”