MicroRNAs (miRs) are regulators of number of cellular process. miRs enclosed within exosomes can be crucial regulators of intercellular signalling and could be an important biomarker of various age-associated disorders. Role of exosomal enclosed miRs in osteoarthritis (OA) chondrocytes and synovial fibroblasts (SFBs) remains poorly studied. Here, we profiled and studied the effect of synovial fluid-derived exosomal miRs on inflammation, survival, proliferation of chondrocyte in correlation with cartilage degeneration. Exosomes were isolated from synovial fluid collected from OA subjects and were analysed by transmission electron microscopy. miRs were isolated and were submitted to microarray profiling. Web-based PCR analysis was done. Chondrocyte proliferation and colony formation assay were performed. Apoptosis study was done by flow cytometer. Gene expression was done by qRT-PCR analysis and protein expression by western blot assay. Rat model of OA was created by operating the knee by anterior cruciate ligament and resection of medial menisci (ACLT + MMx) method. Micro-CT analysis, histological analysis, immunohistochemical staining, and TUNEL assay were also performed. About 17 miRs were found to be expressed differentially in the synovial fluid collected from the control and OA subjects. Microarray analysis confirmed, expression of miR-214-3p was significantly downregulated in the synovial fluid exosome of OA subjects. miR-214-3p mimic promoted proliferation of chondrocyte and suppressed apoptosis. Treatment also inhibited the levels of TNF-α, IL-1β and IL-6. SFB-miR-214-3p exosomes suppressed apoptosis and also inflammation in chondrocytes. In vivo study suggested that SFB-exosomal miR-214-3p from rats suppressed the formation of osteophytes, prevented degeneration of cartilage and exerted anti-inflammatory and anti-apoptotic effect in articular cartilage tissue. The findings suggested that SFB-miR-214-3p exosomes can ameliorate chondrocyte inflammation and degeneration of cartilage tissues. The study confirms therapeutic potential of SFB-miR-214-3p exosomes in treating OA.

Recent studies have indicated that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an ideal therapeutic target for osteoporosis because it affects the differentiation of osteoblasts and osteoclasts. RNA sequencing utilizing multifunctional graphene oxide (GO) nanosheets revealed a correlation between GO nanomaterials and the NLRP3 inflammasome, as well as osteogenic genes in macrophages. This study aimed to construct a bone microenvironment-responsive multifunctional two-dimensional GO coating on the surface of microporous sulfonated polyetheretherketone (SPEEK) via polydopamine modification (SPEEK@PDA-GO). In vitro analysis showed that the SPEEK@PDA-GO implants weakened the STAT3-mediated NLRP3/caspase-1/IL-1β signaling pathway in macrophages and subsequently prevented the formation of an extracellular inflammatory microenvironment, which is crucial for osteoclastogenesis. SPEEK@PDA-GO displayed significantly higher expression of M2 macrophage markers and osteogenic genes, indicating that the multifunctional GO nanosheets could facilitate bone regeneration via their immunomodulatory properties. The ability of SPEEK@PDA-GO to stimulate new bone formation and block bone loss caused by estrogen loss due to ovariectomy was also analyzed. The findings of this study offer valuable information on the possible involvement of the NLRP3 inflammasome in the interaction between the immune system and bone health in patients with osteoporosis.

Wear particle-induced osteoclast over-activation is a major contributor to periprosthetic osteolysis and aseptic loosening, which can cause pathological bone loss and destruction. Hence, inhibiting excessive osteoclast-resorbing activity is an important strategy for preventing periprosthetic osteolysis. Formononetin (FMN) has been shown to have protective effects against osteoporosis, but no previous study has evaluated the effects of FMN on wear particle-induced osteolysis. In this study, we found that FMN alleviated CoCrMo alloy particles (CoPs)-induced bone loss in vivo and inhibited the formation and bone-resorptive function of osteoclasts in vitro. Moreover, we revealed that FMN exerted inhibitory effects on the expression of osteoclast-specific genes via the classical NF-κB and MAPK signaling pathways in vitro. Collectively, FMN is a potential therapeutic agent for the prevention and treatment of periprosthetic osteolysis and other osteolytic bone diseases.