Circular RNA circPDE4D Protects against Osteoarthritis by Binding to miR-103a-3p and Regulating FGF18.

Osteoarthritis (OA) is a common, age-related, and painful disease characterized by cartilage destruction, osteophyte formation, and synovial hyperplasia. This study revealed that circPDE4D, a circular RNA derived from human linear PDE4D, plays a critical role in maintaining the extracellular cellular matrix (ECM) during OA progression. circPDE4D was significantly downregulated in OA cartilage tissues and during stimulation with inflammatory cytokines. The knockdown of circPDE4D predominantly contributed to Aggrecan loss and the upregulation of matrix catabolic enzymes, including MMP3, MMP13, ADAMTS4, and ADAMTS5, but not proliferation or apoptosis. In a murine model of destabilization of the medial meniscus (DMM), the intraarticular injection of circPDE4D alleviated DMM-induced cartilage impairments. Mechanistically, we found that circPDE4D exerted its effect by acting as a sponge for miR-103a-3p and thereby regulated FGF18 expression, which is a direct target of miR-103a-3p. In conclusion, our findings highlight a novel protective role of circPDE4D in OA pathogenesis and indicate that the targeting of the circPDE4D-miR-103a-3p-FGF18 axis might provide a potential and promising approach for OA therapy.

A novel educational tool helps teach intestinal absorption in physiology.

A novel educational tool helps teach intestinal absorption in physiology-We have designed an interesting educational tool to help sophomores learn intestinal absorption in physiology course. In the study group (2019), 51 sophomores from biomedical engineering were encouraged to learn the intestinal absorption knowledge through reading materials and group discussion. Then, using the form of flipped class, they stepped on the podium and simulated and explained the absorption processes with designed paper props as educational tool. In contrast, the control group (2018), 52 sophomores from the same specialty had taken the same professional courses before. The result of theoretical test showed the average score in the study group was higher than that in the control group. The questionnaire analysis showed the positive role of the education tool in their learning efficacy. To sum up, using our tool has achieved better teaching effects than the traditional lecture.

An inducible long noncoding RNA, LncZFHX2, facilitates DNA repair to mediate osteoarthritis pathology.

Cartilage homeostasis is essential for chondrocytes to maintain proper phenotype and metabolism. Because adult articular cartilage is avascular, chondrocytes must survive in low oxygen conditions, and changing oxygen tension can significantly affect metabolism and proteoglycan synthesis in these cells. However, whether long noncoding RNA participate in cartilage homeostasis under hypoxia has not been reported yet. Here, we first identified LncZFHX2 as a lncRNA upregulated under physiological hypoxia in cartilage, specifically by HIF-1α. LncZFHX2 knockdown simultaneously accelerated cellular senescence, targeted multiple components of extracellular matrix metabolism, and increased DNA damage in chondrocytes. Through a series of in vitro and in vivo experiments, we identified that LncZFHX2 performed a novel function that regulated RIF1 expression through forming a transcription complex with KLF4 and promoting chondrocyte DNA repair. Moreover, chondrocyte-conditional knockout of LncZFHX2 accelerated injury-induced cartilage degeneration in vivo. In conclusion, we identified a hypoxia-activated DNA repair pathway that maintains matrix homeostasis in osteoarthritis cartilage.

Metabolite asymmetric dimethylarginine (ADMA) functions as a destabilization enhancer of SOX9 mediated by DDAH1 in osteoarthritis.

Osteoarthritis (OA) is a degenerative disease with a series of metabolic changes accompanied by many altered enzymes. Here, we report that the down-regulated dimethylarginine dimethylaminohydrolase-1 (DDAH1) is accompanied by increased asymmetric dimethylarginine (ADMA) in degenerated chondrocytes and in OA samples. Global or chondrocyte-conditional knockout of ADMA hydrolase DDAH1 accelerated OA development in mice. ADMA induces the degeneration and senescence of chondrocytes and reduces the extracellular matrix deposition, thereby accelerating OA progression. ADMA simultaneously binds to SOX9 and its deubiquitinating enzyme USP7, blocking the deubiquitination effects of USP7 on SOX9 and therefore leads to SOX9 degradation. The ADMA level in synovial fluids of patients with OA is increased and has predictive value for OA diagnosis with good sensitivity and specificity. Therefore, activating DDAH1 to reduce ADMA level might be a potential therapeutic strategy for OA treatment.