The efficacy of Bone Marrow Mesenchymal Stem Cell-derived Exosomes (BMSCs-Exo) in addressing the complexities of Polycystic Ovary Syndrome (PCOS) has been explored in a controlled experimental study using a DHEA-induced PCOS model in 6-8-week-old female NMRI mice. This research undertook an in vivo approach with fifteen female murine subjects to investigate the potential of BMSCs-Exo in promoting vascular regeneration and alleviating the adverse effects associated with PCOS. Through a strategic intervention, the study aimed to modulate the pathophysiological markers of oxidative stress and inflammation that are hallmark features of PCOS. Remarkably, the administration of BMSCs-Exo led to decreased CD31 expression in ovarian tissues, suggesting reduced angiogenesis and endothelial activation. Moreover, a significant reduction in pro-inflammatory cytokines and oxidative stress markers was noted, aligning closely with the metrics observed in the control group. These findings illuminate a promising therapeutic avenue utilizing BMSCs-Exo to recalibrate angiogenic, inflammatory, and oxidative stress responses in PCOS. This research not only contributes to the current understanding of PCOS management but also opens new doors for innovative clinical treatments.

Several long non-coding RNAs (lncRNAs) are dysregulated in chronic periodontitis (CP).

The study aimed to elucidate the molecular mechanisms and clinical significance of lncRNA EPB41L4A antisense RNA 1 (EPB41L4A-AS1) in CP.

This study enrolled 101 patients with CP and 90 subjects with healthy periodontal tissues. Patients with CP were categorized according to severity. The expression of EPB41L4A-AS1 and osteogenic markers in the lipopolysaccharide (LPS)-induced human periodontal ligament cells (hPDLCs) was assessed using real-time quantitative reverse transcription PCR (RT-qPCR). The diagnostic significance of EPB41L4A-AS1 was evaluated using receiver operating characteristic (ROC) analysis. The levels of inflammatory factors were measured using an enzyme-linked immunosorbent assay. Cell proliferation and apoptosis were analyzed using cell counting kit -8 and flow cytometry, respectively. The interaction between EPB41L4A-AS1 and microRNAs was verified using dual luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays.

EPB41L4A-AS1 was downregulated in the gingival sulcus fluid of patients with CP and LPS-induced hPDLCs. Additionally, EPB41L4A-AS1 could distinguish patients with CP from control subjects with sensitivity (88.12%) and specificity (81.11%). The expression of EPB41L4A-AS1 was downregulated in patients with severe CP. EPB41L4A-AS1 downregulation was directly correlated with severe clinical indicators and inversely correlated with inflammatory indicators. The overexpression of EPB41L4A-AS1 promoted the proliferation and osteogenic differentiation of hPDLCs and mitigated LPS-induced inflammation. Mechanistically, EPB41L4A-AS1 directly targets and downregulates miR-214-3p expression, resulting in the upregulation of Yes1-associated transcriptional regulator (YAP1) levels. The overexpression of miR-214-3p partially suppressed the effects of EPB41L4A-AS1 on LPS-induced hPDLC injury and osteogenic differentiation.

The overexpression of EPB41L4A-AS1 suppressed LPS-induced hPDLC injury and enhanced osteogenic differentiation through the miR-214-3p/YAP1 axis. Thus, EPB41L4A-AS1 is a novel diagnostic marker and a therapeutic target for CP.

Spinal fusion surgery remains a significant challenge due to limitations in current bone graft materials, particularly in terms of bioactivity, integration, and safety. This study presents an innovative approach using an injectable hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) hydrogel combined with stromal vascular fraction (SVF) and low-dose recombinant human BMP-2 (rhBMP-2) to enhance osteodifferentiation and angiogenesis. Through a series of in vitro studies and preclinical models involving rats and minipigs, we demonstrated that the hydrogel system enables the sustained release of rhBMP-2, resulting in significantly improved bone density and integration, alongside reduced inflammatory responses. The combination of rhBMP-2 and SVF in this injectable formulation yielded superior spinal fusion outcomes, with enhanced mechanical properties and increased bone mass in both small and large animal models. These findings suggest that this strategy offers a promising and safer alternative for spinal fusion, with strong potential for clinical application.

Although fine dust is linked to numerous health issues, including cardiovascular, neurological, respiratory, and cancerous diseases, research on its effects on oral health remains limited. In this study, we investigated the protective effects of mature hemp stem extract-induced exosomes (MSEIEs) on periodontal cells exposed to fine dust. Using various methods, including microRNA profiling, PCR, flow cytometry, immunocytochemistry, ELISA, and Alizarin O staining, we found that MSE treatment upregulated key microRNAs, such as hsa-miR-122-5p, hsa-miR-1301-3p, and hsa-let-7e-5p, associated with vital biological functions. MSEIEs exhibited three primary protective functions: suppressing inflammatory genes while activating anti-inflammatory ones, promoting the differentiation of periodontal ligament stem cells (PDLSCs) into osteoblasts and other cells, and regulating LL-37 and MCP-1 expression. These findings suggest that MSEIEs have potential as functional biomaterials for applications in pharmaceuticals, cosmetics, and food industries.

Human osteogenic differentiation is a complex and well-orchestrated process which involves a plethora of molecular players and cellular processes. A growing number of studies have underlined that circular RNAs (circRNAs) play an important regulatory role during human osteogenic differentiation. CircRNAs are single-stranded, covalently closed non-coding RNA molecules that are acquiring increased attention as epigenetic regulators of gene expression. Given their intrinsic high conformational stability, abundance, and specificity, circRNAs can undertake various biological activities in order to regulate multiple cellular processes, including osteogenic differentiation. The most recent evidence indicates that circRNAs control human osteogenesis by preventing the inhibitory activity of miRNAs on their downstream target genes, using a competitive endogenous RNA mechanism. The aim of this review is to draw attention to the currently known regulatory mechanisms of circRNAs during human osteogenic differentiation. Specifically, we provide an understanding of recent advances in research conducted on various human mesenchymal stem cell types that underlined the importance of circRNAs in regulating osteogenesis. A comprehensive understanding of the underlying regulatory mechanisms of circRNA in osteogenesis will improve knowledge on the molecular processes of bone growth, resulting in the potential development of novel preclinical and clinical studies and the discovery of novel diagnostic and therapeutic tools for bone disorders.

The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells (PSCs) into osteoblasts or chondrocytes; however, the underlying mechanisms remain unclear.

To determine the effect of hypoxia on PSCs, and the expression of microRNA-584-5p (miR-584-5p) and RUNX family transcription factor 2 (RUNX2) in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxia-induced osteogenic differentiation of PSCs.

In this study, we isolated primary mouse PSCs and stimulated them with hypoxia, and the characteristics and functional genes related to PSC osteogenic differentiation were assessed. Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.

Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules, intracellular calcium ion levels, and alkaline phosphatase (ALP) activity in PSCs. Osteogenic differentiation-related factors such as RUNX2, bone morphogenetic protein 2, hypoxia-inducible factor 1-alpha, and ALP were upregulated; in contrast, miR-584-5p was downregulated in these cells. Furthermore, upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation. RUNX2 was the target gene of miR-584-5p, antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.

Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.