Diagnostic biomarkers in knee osteoarthritis: Based on bioinformatics and experimental verification in vivo and in vitro.

BACKGROUND: Knee osteoarthritis (KOA) is a multifactorial whole-joint disease with a high rate of disability. Considering the complexity of KOA, there is an urgent need to discover new molecular pathological markers and multi-target treatment strategies. METHODS: Two datasets, GSE51588 and GSE57218, were downloaded from the Gene Expression Omnibus database and screened for differentially expressed genes (DEGs) using the Gene Expression Omnibus 2R (GEO2R). Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed. A protein-protein interaction (PPI) network was constructed and hub genes were identified using Molecular Complex Detection (MCODE). Receiver-operating characteristic curves (ROC) were plotted for the genes, and their prognostic values were evaluated. The expression levels of the hub genes in the monosodium iodoacetate (MIA)-induced KOA rat model and lipopolysaccharide (LPS)-stimulated C28/I2 cells were verified using reverse transcription quantitative real-time PCR (RT-qPCR). RESULTS: Overall, 33 DEGs were up-regulated and 6 DEGs were down-regulated in the two datasets. A total of 12 hub genes were identified, including COL15A1, THY1, COL1A1, COL5A1, CTHRC1, MXRA5, FN1, COL1A2, COL3A1, SPARC, COL8A1, and COL2A1, which all could be used as biomarkers to differentiate KOA samples from healthy controls. More importantly, we found that THY1, CTHRC1, SPARC, and COL8A1 were significantly upregulated in vivo and in vitro compared with the controls (p < .01). CONCLUSIONS: The expression levels of THY1, CTHRC1, SPARC, and COL8A1 were elevated and had good prognostic values as biomarkers in KOA.

Transplantation of MiR-28-5p-Modified BMSCs Promotes Functional Recovery After Spinal Cord Injury.

Traumatic spinal cord injury (TSCI) is a prevalent central nervous system condition that imposes a significant burden on both families and society, affecting more than 2 million people worldwide. Recently, there has been increasing interest in bone marrow mesenchymal stem cell (BMSC) transplantation as a promising treatment for spinal cord injury (SCI) due to their accessibility and low immunogenicity. However, the mere transplantation of BMSCs has limited capacity to directly participate in the repair of host spinal cord nerve function. MiR-28-5p, identified as a key differentially expressed miRNA in spinal cord ischemia-reperfusion injury, exhibits differential expression and regulation in various neurological diseases. Nevertheless, its involvement in this process and its specific regulatory mechanisms in SCI remain unclear. Therefore, this study aimed to investigate the potential mechanisms through which miR-28-5p promotes the neuronal differentiation of BMSCs both in vivo and in vitro. Our results indicate that miR-28-5p may directly target Notch1, thereby facilitating the neuronal differentiation of BMSCs in vitro. Furthermore, the transplantation of lentivirus-mediated miR-28-5p-overexpressed BMSCs into SCI rats effectively improved footprint tests and Basso, Beattie, and Bresnahan (BBB) scores, ameliorated histological morphology (hematoxylin-eosin [HE] and Nissl staining), promoted axonal regeneration (MAP2 and growth-associated protein 43 [GAP43]), and facilitated axonal remyelination (myelin basic protein [MBP]). These findings may suggest that miR-28-5p-modified BMSCs could serve as a therapeutic target to enhance the behavioral and neurological recovery of SCI rats.

Tauroursodeoxycholic Acid Inhibited Apoptosis and Oxidative Stress in H2O2-Induced BMSC Death via Modulating the Nrf-2 Signaling Pathway: the Therapeutic Implications in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a prevalent and significant injury to the central nervous system, resulting in severe consequences. This injury is characterized by motor, sensory, and excretory dysfunctions below the affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a potential treatment for SCI. However, the low survival as well as the differentiation rates of BMSCs within the spinal cord microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (TUDCA), an active ingredient found in bear bile, has demonstrated its neuroprotective, antioxidant, and antiapoptotic effects on SCI. Thus, the present study was aimed to study the possible benefits of combining TUDCA with BMSC transplantation using an animal model of SCI. The results showed that TUDCA significantly enhanced BMSC viability and reduced apoptosis (assessed by Annexin V-FITC, TUNEL, Bax, Bcl-2, and Caspase-3) as well as oxidative stress (assessed by ROS, GSH, SOD, and MDA) both in vitro and in vivo. Additionally, TUDCA accelerated tissue regeneration (assessed by HE, Nissl, MAP2, MBP, TUJ1, and GFAP) and improved functional recovery (assessed by BBB score) following BMSC transplantation in SCI. These effects were mediated via the Nrf-2 signaling pathway, as evidenced by the upregulation of Nrf-2, NQO-1, and HO-1 expression levels. Overall, these results indicate that TUDCA could serve as a valuable adjunct to BMSC transplantation therapy for SCI, potentially enhancing its therapeutic efficacy.