miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway.

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients.

Prognostic Role of TIGIT Expression in Patients with Solid Tumors: A Meta-Analysis.

BACKGROUND: T cell immunoglobulin and ITIM domain (TIGIT) is a recently identified immunosuppressive receptor. The expression levels of TIGIT affect the prognosis of patients with solid tumors. To fully comprehend the role of TIGIT on the prognosis of patients with solid tumors, we conducted a meta-analysis. METHODS: We performed an online search of PubMed, Embase, Web of Science (WOS), and MEDLINE databases for literature published till March 31, 2021. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature, and Stata 16.0 and Engauge Digitizer 4.1 software were used for data analysis. RESULTS: Our literature search identified eight papers comprising 1426 patients with solid tumors. Increased expression of TIGIT was associated with poor prognosis. High expression of TIGIT was a risk factor for overall survival (OS) {hazard ratio (HR) = 1.66, 95% confidence interval (CI) [1.26, 2.20], P < 0.001} and progression-free survival (PFS) (HR = 1.44, 95% CI [1.15, 1.81], P = 0.01). We performed subgroup analysis to explore the source of heterogeneity, colorectal cancer (HR = 2.07, 95% CI [0.23, 18.82], P = 0.518), lung cancer (HR = 1.29, 95% CI [0.96, 1.72], P = 0.094), esophageal cancer (HR = 1.70, 95% CI [1.20, 2.40], P = 0.003), and other cancers (HR = 1.83, 95% CI [1.25, 2.68], P = 0.002). In addition to cancer type, expression location, sample size, and different statistical analysis methods are also considered the possible causes of heterogeneity between studies. Funnel plots suggested no publication bias for OS (P = 0.902), and Egger's test supported this conclusion (P = 0.537). CONCLUSION: TIGIT expression was associated with OS and PFS in patients with solid tumors. Patients with elevated TIGIT expression have a shorter OS and PFS, and TIGIT expression could be a novel biomarker for prognosis prediction and a valuable therapeutic target for solid tumors.

Allogeneic adipose-derived mesenchymal stem cells promote the expression of chondrocyte redifferentiation markers and retard the progression of knee osteoarthritis in rabbits.

Osteoarthritis (OA) is a progressively degenerative disease of joints. In vitro culture of chondrocytes results in dedifferentiation, which is characterized by the development of fibroblast phenotypes, reduced ability to produce cartilage extracellular matrix (ECM) and increase the expression of molecular markers Col1a1, Col10a1 and Runx2. Redifferentiation of chondrocytes is indicated by increased expression of the molecular markers Col2a1, Aggrecan and Sox9. In the current study, we investigated the effects of allogeneic rabbit adipose-derived mesenchymal stem cells (ADSCs) on articular chondrocytes, and explored the therapeutic effect of ADSCs on damaged articular cartilage at different stages in a rabbit OA model. In vitro, the proliferation and migration of primary articular chondrocytes were enhanced by cocultured rabbit ADSCs, and the expression of redifferentiation markers in chondrocytes cocultured with ADSCs was increased at both the mRNA and protein levels, while the expression of dedifferentiation markers was decreased. In vivo, the rabbit model of OA was established by anterior cruciate ligament transection (ACLT) with complete medial meniscectomy (MMx). Two weeks after surgery, ADSCs were used for OA rabbit treatment. Intra-articular injection of ADSCs gradually alleviated articular cartilage destruction, decreased Osteoarthritis Research Society International (OARSI) and Mankin scores, and reduced MMP13 expression at different stages in the rabbit model of OA. During the experiment, allogeneic ADSCs did not cause any adverse events. The current study demonstrates the effects and molecular mechanisms of ADSCs on articular chondrocytes and provides a favorable reference for clinical OA treatment with mesenchymal stem cells (MSCs) derived from adipose tissue.