The role of WNT and IL-1 signaling in osteoarthritis: therapeutic implications for platelet-rich plasma therapy

Tonutti, Antonio; Granata, Valentina; Marrella, Veronica; Sobacchi, Cristina; Ragusa, R. M.; Sconza, Cristiano; Rani, Nicola; Matteo, Berardo Di; Ceribelli, Angela

doi:10.3389/fragi.2023.1201019

Cited by 9 publications

(6 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-1β is one of the most potent stimulators of cartilage breakdown. It inhibits synthesis of type II collagen and proteoglycans and promotes the synthesis of MMPs, ADAMTS 50 and IL-6; 51 it is interesting that expression of TNFα was not detected in most samples. Our data also showed IL-7 as another proinflammatory cytokine whose expression increases in late passage cultures.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic changes during the replicative senescence of human articular chondrocytes

Atasoy-Zeybek,

Hawse,

Nagelli

et al. 2023

Preprint

View full text Add to dashboard Cite

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability worldwide. Aging is a major risk factor for OA, but the specific mechanisms underlying this connection remain unclear. Although chondrocytes rarely divide in adult articular cartilage, they undergo replicative senescencein vitrowhich provides an opportunity to study changes related to aging under controlled laboratory conditions. In this pilot study, we performed bulk RNA sequencing on early- and late-passage human articular chondrocytes to identify transcriptomic changes associated with cellular aging. Chondrocytes were isolated from the articular cartilage of three donors, two with OA (age 70-80 years) and one with healthy cartilage (age 26 years). Chondrocytes were serially passaged until replicative senescence and RNA extracted from early- and late-passage cells. Principal component analysis of all genes showed clear separation between early- and late- passage chondrocytes, indicating substantial age-related differences in gene expression. Differentially expressed genes (DEGs) analysis confirmed distinct transcriptomic profiles between early- and late-passage chondrocytes. Hierarchical clustering revealed contrasting expression patterns between the two isolates from osteoarthritic samples and the healthy sample. Focused analysis of DEGs on transcripts associated with turnover of the extra-cellular matrix and the senescence-associated secretory phenotype (SASP) showed consistent downregulation of Col2A1 and ACAN, and upregulation of MMP19, ADAMTS4, and ADAMTS8 in late passage chondrocytes across all samples. SASP components including IL-1α, IL-1β, IL-6, IL-7, p16INK4A(CDKN2A) and CCL2 demonstrated significant upregulation in late passage chondrocytes originally isolated from OA samples. Pathway analysis between sexes with OA revealed shared pathways such as extracellular matrix (ECM) organization, collagen formation, skeletal and muscle development, and nervous system development. Sex-specific differences were observed, with males showing distinctions in ECM organization, regulation of the cell cycle process as well as neuron differentiation. In contrast, females exhibited unique variations in the regulation of the cell cycle process, DNA metabolic process, and the PID-PLK1 pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptomic changes during the replicative senescence of human articular chondrocytes

Atasoy-Zeybek,

Hawse,

Nagelli

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Various physical agent modalities are also utilized in the treatment of OA with a low level of evidence, but their effects are limited [ 8 ]. New investigations are ongoing, such as intra-articular Botulinum toxin injection, which has shown promising results in the early stages, aiming to manage pain in OA [ 9 ], Over time, intraarticular injections that include corticosteroids, ozone, HA, and platelet-rich plasma (PRP) [ 10 – 14 ] have started to be preferred instead of NSAID due to less systemic side effects and faster pain relief effects [ 15 ]. The intra-articular HA injection, which is a commonly utilized treatment approach, has been demonstrated to be effective and has been shown to reduce the necessity for analgesic use [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of single and multiple hyaluronic acid injections at different concentrations with high molecular weight in the treatment of knee osteoarthritis

Safali,

Ertaş,

Özdemir

et al. 2024

BMC Musculoskelet Disord

View full text Add to dashboard Cite

Background Knee osteoarthritis is severe progressive and most commonly diagnosed articular disease and its incidence is increasing around the world depending on age. This pathologic condition which limits daily activity of patients can be characterized by degeneration of cartilage and inflammation. Although non-steroidal anti-inflammatory (NSAII) agents and other analgesics are routinely used treatment options, the potential effects of intraarticular injections including hyaluronic acid (HA) have also been demonstrated by various studies. However, few studies compare the efficacy of a single high molecular weight (HMW) high dose and a triple HMW low dose. This study aimed to compare the efficacy of single high molecular weight (HMW) high dose (2 mL / 60 mg) and triple HMW low dose (2 mL /30 mg) intra-articular injection of HA in knee osteoarthritis (OA) patients by evaluating function and pain parameters during 12 months. Methods This is a single-center, retrospective clinical study that included and involved 128 patients. Group I (n=64) patients received triple 30 mg HA injections (SEMICAL®) with one-week intervals, while Group II (n=64) patients received a single 60 mg HA injection (SEMICAL®). Lequesne Index, WOMAC and VAS scores were recorded to assess pain and function during a 12-month period. Results There was no significant difference in characteristics of patient demographics. Our finding indicate that WOMAC, VAS score, and Lequesne Index values during follow-up visits exhibited a decrease, signifying improvement in the clinical condition. Notably, scores were significantly more favorable with the 30 mg of HA injection compared to the 60 mg of HA injection. Conclusion This study suggests that the triple low-dose injection of HMW HA is more effective in improving WOMAC, VAS scores and Lequesne Index values than a single high-dose injection.

show abstract

“…However, since the 1980s, it has become apparent that an inflammatory component plays a significant role in the pathogenic process. Consequently, the name of the disease has been revised to reflect this newfound understanding [9].…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

Coppola,

Greco,

Munir

et al. 2024

CIMB

View full text Add to dashboard Cite

Osteoarthritis (OA) stands as a prevalent and progressively debilitating clinical condition globally, impacting joint structures and leading to their gradual deterioration through inflammatory mechanisms. While both non-modifiable and modifiable factors contribute to its onset, numerous aspects of OA pathophysiology remain elusive despite considerable research strides. Presently, diagnosis heavily relies on clinician expertise and meticulous differential diagnosis to exclude other joint-affecting conditions. Therapeutic approaches for OA predominantly focus on patient education for self-management alongside tailored exercise regimens, often complemented by various pharmacological interventions primarily targeting pain alleviation. However, pharmacological treatments typically exhibit short-term efficacy and local and/or systemic side effects, with prosthetic surgery being the ultimate resolution in severe cases. Thus, exploring the potential integration or substitution of conventional drug therapies with natural compounds and extracts emerges as a promising frontier in enhancing OA management. These alternatives offer improved safety profiles and possess the potential to target specific dysregulated pathways implicated in OA pathogenesis, thereby presenting a holistic approach to address the condition’s complexities.

show abstract

The role of WNT and IL-1 signaling in osteoarthritis: therapeutic implications for platelet-rich plasma therapy

Cited by 9 publications

References 84 publications

Transcriptomic changes during the replicative senescence of human articular chondrocytes

Transcriptomic changes during the replicative senescence of human articular chondrocytes

Evaluation of single and multiple hyaluronic acid injections at different concentrations with high molecular weight in the treatment of knee osteoarthritis

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

Contact Info

Product

Resources

About