Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient’s quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1β were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.

Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression

Objective: Osteoarthritis (OA) is the most common chronic degenerative joint disease, which represents the leading cause of age-related disability. Here, this study aimed to depict the intercellular heterogeneity of OA synovial tissues.Methods: Single-cell RNA sequencing (scRNA-seq) data were preprocessed and quality controlled by the Seurat package. Cell cluster was presented and cell types were annotated based on the mRNA expression of corresponding marker genes by the SingleR package. Cell-cell communication was assessed among different cell types. After integrating the GSE55235 and GSE55457 datasets, differentially expressed genes were identified between OA and normal synovial tissues. Then, differentially expressed marker genes were overlapped and their biological functions were analyzed.Results: Totally, five immune cell subpopulations were annotated in OA synovial tissues including macrophages, dendritic cells, T cells, monocytes and B cells. Pseudo-time analysis revealed the underlying evolution process in the inflammatory microenvironment of OA synovial tissue. There was close crosstalk between five cell types according to the ligand-receptor network. The genetic heterogeneity was investigated between OA and normal synovial tissues. Furthermore, functional annotation analysis showed the intercellular heterogeneity across immune cells in OA synovial tissues.Conclusion: This study offered insights into the heterogeneity of OA, which provided in-depth understanding of the transcriptomic diversities within synovial tissue. This transcriptional heterogeneity may improve our understanding on OA pathogenesis and provide potential molecular therapeutic targets for OA.

Degenerative joint disease induced by repeated intra-articular injections of monosodium urate crystals in rats as investigated by translational imaging

The objective of this work was to assess the consequences of repeated intra-articular injection of monosodium urate (MSU) crystals with inflammasome priming by lipopolysaccharide (LPS) in order to simulate recurrent bouts of gout in rats. Translational imaging was applied to simultaneously detect and quantify injury in different areas of the knee joint. MSU/LPS induced joint swelling, synovial membrane thickening, fibrosis of the infrapatellar fat pad, tidemark breaching, and cartilage invasion by inflammatory cells. A higher sensitivity to mechanical stimulus was detected in paws of limbs receiving MSU/LPS compared to saline-injected limbs. In MSU/LPS-challenged joints, magnetic resonance imaging (MRI) revealed increased synovial fluid volume in the posterior region of the joint, alterations in the infrapatellar fat pad reflecting a progressive decrease of fat volume and fibrosis formation, and a significant increase in the relaxation time T2 in femoral cartilage, consistent with a reduction of proteoglycan content. MRI also showed cyst formation in the tibia, femur remodeling, and T2 reductions in extensor muscles consistent with fibrosis development. Repeated intra-articular MSU/LPS injections in the rat knee joint induced pathology in multiple tissues and may be a useful means to investigate the relationship between urate crystal deposition and the development of degenerative joint disease.

Correlation of MRI and arthroscopic findings with clinical outcome in temporomandibular joint disorders: a retrospective cohort study

Background Arthroscopy is a minimally invasive diagnostic tool and treatment strategy in patients suffering from temporomandibular disorders (TMD) when conservative treatment fails. This study aimed to find specific variables on pre-operative MRI or during arthroscopy that could predict success of arthroscopic lysis and lavage. Methods This retrospective analysis compared pre-operative maximum interincisal opening (MIO), pain and main complaint (pain, limited MIO or joint sounds) with results at short-term and medium-term follow-up (ST and MT respectively). Different variables scored on MRI or arthroscopy were used to make a stepwise regression model, subsequently a combined analysis was conducted using variables from both MRI and arthroscopy. Results A total of 47 patients (50 joints) met the inclusion criteria. The main complaint improved by 62 and 53% at ST and MT respectively. The absolute or probable absence of a crumpled disc scored on MRI predicted success at ST and MT (p = 0.0112 and p = 0.0054), and remained significant at MT in the combined analysis (p = 0.0078). Arthroscopic findings of degenerative joint disease predicted success at ST (p = 0.0178), absolute or probable absence of discal reduction scored during arthroscopy significantly predicted success in the combined analysis at ST (p = 0.0474). Conclusion To improve selection criteria for patients undergoing an arthroscopic lysis and lavage of the TMJ, future research might focus on variables visualized on MRI. Although more research is needed, disc shape and in particular the absolute or probable absence of a crumpled disc might be used as predictive variable for success.

Ezetimibe prevents IL-1β-induced inflammatory reaction in mouse chondrocytes via modulating NF-κB and Nrf2/HO-1 signaling crosstalk

Background: Osteoarthritis, a type of age-related, chronic, degenerative joint disease. Ezetimibe, a cholesterol absorption inhibitor, is widely used for the treatment of various diseases. The role of ezetimibe in osteoarthritis remains unclear. Objective: This study aimed to explored the anti-inflammation effect of ezetimibe on mouse chondrocytes. Method: In the present study, ELISA, qPCR and western blot analysis were performed to evaluate the anti-inflammatory effects of ezetimibe. In addition, enzymes that are highly associated with the anabolism and catabolism of the extracellular matrix of the articular cartilage were also evaluated. Results: Treatment with ezetimibe attenuated the IL-1β-induced degradation of the extracellular matrix, including aggrecan and collagen II. Ezetimibe also attenuated the IL-1β-induced expression levels of MMP3, MMP13 and ADAMTS5, thus exerting protective effects against IL-1β-induced extracellular matrix degradation. The complex mechanism of the anti-inflammatory reaction contributed to the activation of the Nrf2/HO-1 pathway and the suppression of the NF-κB pathway. Conclusion: On the whole, the present study demonstrates that ezetimibe may be a promising agent for further osteoarthritis therapy

Autophagy and Polyphenols in Osteoarthritis: A Focus on Epigenetic Regulation

Autophagy is an intracellular mechanism that maintains cellular homeostasis in different tissues. This process declines in cartilage due to aging, which is correlated with osteoarthritis (OA), a multifactorial and degenerative joint disease. Several studies show that microRNAs regulate different steps of autophagy but only a few of them participate in OA. Therefore, epigenetic modifications could represent a therapeutic opportunity during the development of OA. Besides, polyphenols are bioactive components with great potential to counteract diseases, which could reverse altered epigenetic regulation and modify autophagy in cartilage. This review aims to analyze epigenetic mechanisms that are currently associated with autophagy in OA, and to evaluate whether polyphenols are used to reverse the epigenetic alterations generated by aging in the autophagy pathway.

Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1β) and tumor necrosis factor α (TNF-α) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment.

Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

Osteoarthritis (OA) is a common degenerative joint disease and is a leading cause of disability and reduced quality of life worldwide. There are currently no clinical treatments that can stop or slow down OA. Drugs have pain-relieving effects, but they do not slow down the course of OA and their long-term use can lead to serious side effects. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Autophagy is an intracellular protective mechanism, and targeting autophagy-related pathways has been found to prevent and treat various diseases. Attenuation of the autophagic pathway has now been found to disrupt cartilage homeostasis and plays an important role in the development of OA. Therefore, modulation of autophagic signaling pathways mediating cartilage homeostasis has been considered as a potential therapeutic option for OA. Phytochemicals are active ingredients from plants that have recently been found to reduce inflammatory factor levels in cartilage as well as attenuate chondrocyte apoptosis by modulating autophagy-related signaling pathways, which are not only widely available but also have the potential to alleviate the symptoms of OA. We reviewed preclinical studies and clinical studies of phytochemicals mediating autophagy to regulate cartilage homeostasis for the treatment of OA. The results suggest that phytochemicals derived from plant extracts can target relevant autophagic pathways as complementary and alternative agents for the treatment of OA if subjected to rigorous clinical trials and pharmacological tests.

Intra-Articular Drug Delivery for Osteoarthritis Treatment

Osteoarthritis (OA) is the most prevalent degenerative joint disease affecting millions of people worldwide. Currently, clinical nonsurgical treatments of OA are only limited to pain relief, anti-inflammation, and viscosupplementation. Developing disease-modifying OA drugs (DMOADs) is highly demanded for the efficient treatment of OA. As OA is a local disease, intra-articular (IA) injection directly delivers drugs to synovial joints, resulting in high-concentration drugs in the joint and reduced side effects, accompanied with traditional oral or topical administrations. However, the injected drugs are rapidly cleaved. By properly designing the drug delivery systems, prolonged retention time and targeting could be obtained. In this review, we summarize the drugs investigated for OA treatment and recent advances in the IA drug delivery systems, including micro- and nano-particles, liposomes, and hydrogels, hoping to provide some information for designing the IA injected formulations.