Long Non-Coding RNA (LncRNA) CAIF is Downregulated in Osteoarthritis and Inhibits LPS-Induced Interleukin 6 (IL-6) Upregulation by Downregulation of MiR-1246.

BACKGROUND Osteoarthritis (OA) affects about 40% of people older than 40 years of age, and the mechanism is not well understood. Long non-coding RNA (lncRNA) CAIF is a recently identified critical player in myocardial infarction, while its role in other human diseases is unclear. The present study aimed to investigate the role of CAIF in OA. MATERIAL AND METHODS Levels of CAIF in synovial fluid of OA patients (n=60) and healthy controls (n=60) were measuring by performing quantitative real-time polymerase chain reaction (qRT-PCR). MiR-1246 and interleukin (IL)-6 levels in synovial fluid were measured by performing qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell apoptosis analysis was performed after CHON-001 cells were treated with 500 mg/mL lipopolysaccharide (LPS) for 24 hours. RESULTS We found that CAIF in synovial fluid was downregulated in OA patients and inversely correlated with miR-1246 and IL-6. Downregulated CAIF distinguished OA patients from healthy controls. In cells of chondrogenic cell line CHON-001, CAIF overexpression mediated the inhibited expression of miR-1246 and secretion of IL-6, while miR-1246 overexpression reduced the effects of CAIF overexpression on IL-6 secretion. In addition, CAIF overexpression inhibited the apoptosis of CHON-001 cells under LPS treatment, while miR-1246 overexpression attenuated the effects of CAIF overexpression. CONCLUSIONS Therefore, CAIF may downregulate miR-1246 to improve OA.

Ectopic osteogenesis and scaffold biodegradation of nano-hydroxyapatite-chitosan in a rat model.

The bone-formation and scaffold-biodegradation processes have not been fully characterized. This study aimed to determine the osteogenic ability of nHA-CS osteo-induced bone marrow mesenchymal stem cell (BMSC) composites and to explore the relationship between bone formation and scaffold biodegradation. The nHA-CS osteo-induced BMSC composites (nHA-CS+cells group) and the nHA-CS scaffolds (nHA-CS group) were implanted into the femoral spatium intermusculare of SD rats. At 2, 4, 6, 8, and 12 weeks post-implantation, the rat femurs were scanned using computerized tomography (CT), and the CT values of the implants were measured and comparatively analyzed. The implants were then harvested and subjected to hematoxylin and eosin (HE) and Masson's trichrome staining, and the percentages of bone area, scaffold area and collagen area were compared between the two groups. The CT values of the implants were higher in the nHA-CS+cells group than the nHA-CS group at the same time points (P < 0.05). Histological analysis revealed that de novo bone and collagen formation in the pores of the scaffolds gradually increased from 2 weeks post-implantation in both groups and that the scaffold gradually degraded as bone formation proceeded. However, more de novo bone and collagen formation and scaffold degradation occurred in the nHA-CS+cells group than in the nHA-CS group at the same time points (P < 0.05). In conclusion, nHA-CS osteo-induced BMSC composites are promising bone tissue engineering substitutes, and osteo-induced BMSCs can significantly enhance the osteogenic ability and play an active role in the degradation of nHA-CS scaffolds on par with bone formation.

Ectopic osteogenesis and scaffold biodegradation of tissue engineering bone composed of chitosan and osteo-induced bone marrow mesenchymal stem cells in vivo.

BACKGROUND: Chitosan (CS) scaffolds combined with osteogenically induced bone marrow mesenchymal stem cells (BMSCs) have been proved to be promising substitutes for repairing bone defects. Nevertheless, the bone-forming and scaffold-biodegrading processes are seldom studied. This study aimed to determine the osteogenic ability of CS/osteo-induced BMSC composites by observing the bone-forming process and explore the relationship between bone formation and scaffold biodegradation. METHODS: The CS/osteo-induced BMSC composites (CS+cells group) and the CS scaffolds (CS group) were, respectively, implanted into SD rat thigh muscles. At 2, 4, 6, 8, and 12 weeks postoperatively, the rat femurs were scanned by CT, and the CT values of the implants were measured and comparatively analyzed. Subsequently, the implants were harvested and stained with hematoxylin and eosin and Masson trichrome, and the percentages of bone area, scaffold area, and collagen area were calculated and compared between the two groups. RESULTS: The imaging results showed that the densities of implants of the two groups gradually increased along with time, but the CT values of implants in the CS+cells group were much higher than in the CS group at the same time point (P < 0.05). The histological results showed that the de novo bone and collagen formed in the pores of the scaffolds and gradually increased since 2 weeks postoperation in both groups, and the scaffold gradually degraded along with the boneforming process. However, the comparative analysis results showed that the CS+cells group gained more de novo bone and collagen formation and had less scaffold than the CS group at the same time point (P < 0.05). CONCLUSION: The CS/osteo-induced BMSC composites are excellent bone tissue engineering substitutes, and the scaffold biodegradation is accordant with the bone formation.