Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1ß-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies.

Osteoarthritis (OA) is a degenerative joint disease, whose progression is closely related to the inflammatory environment. Urolithin A (UA), a natural metabolite of a class of compounds (ellagitannins and ellagic acid) found in pomegranates and other fruits and nuts, has been proved to exert anti-inflammatory effects in a variety of diseases. However, the exact role of UA in OA development is still unclear. In the present study, we examined the latent mechanism of UA and its protective role in the progression of OA by both in vitro and in vivo experiments. In vitro, UA inhibited the interleukin-1 beta (IL-1ß) induced over-production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in a concentration-dependent manner in human OA chondrocytes. Furthermore, by downregulating the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), UA attenuated the degradation of the extracellular matrix (ECM) induced by IL-1ß. Mechanistically, UA was found to suppress the activation of PI3K/Akt/NF-κB pathways. In vivo, in a surgically induced mouse OA model, UA-induced protective effects in OA development could be detected. In summary, this research suggested that UA may be adopted as a new therapeutic agent for the treatment of OA.

Comparison of reconstruction plate screw fixation and percutaneous cannulated screw fixation in treatment of Tile B1 type pubic symphysis diastasis: a finite element analysis and 10-year clinical experience.

OBJECTIVE: The objective of this study is to compare the biomechanical properties and clinical outcomes of Tile B1 type pubic symphysis diastasis (PSD) treated by percutaneous cannulated screw fixation (PCSF) and reconstruction plate screw fixation (RPSF). MATERIALS AND METHODS: Finite element analysis (FEA) was used to compare the biomechanical properties between PCSF and RPSF. CT scan data of one PSD patient were used for three-dimensional reconstructions. After a validated pelvic finite element model was established, both PCSF and RPSF were simulated, and a vertical downward load of 600 N was loaded. The distance of pubic symphysis and stress were tested. Then, 51 Tile type B1 PSD patients (24 in the PCSF group; 27 in the RPSF group) were reviewed. Intra-operative blood loss, operative time, and the length of the skin scar were recorded. The distance of pubic symphysis was measured, and complications of infection, implant failure, and revision surgery were recorded. The Majeed scoring system was also evaluated. RESULTS: The maximum displacement of the pubic symphysis was 0.408 and 0.643 mm in the RPSF and PCSF models, respectively. The maximum stress of the plate in RPSF was 1846 MPa and that of the cannulated screw in PCSF was 30.92 MPa. All 51 patients received follow-up at least 18 months post-surgery (range 18-54 months). Intra-operative blood loss, operative time, and the length of the skin scar in the PCSF group were significantly different than those in the RPSF group. No significant differences were found in wound infection, implant failure, rate of revision surgery, distance of pubic symphysis, and Majeed score. CONCLUSION: PCSF can provide comparable biomechanical properties to RPSF in the treatment of Tile B1 type PSD. Meanwhile, PCSF and RPSF have similar clinical and radiographic outcomes. Furthermore, PCSF also has the advantages of being minimally invasive, has less blood loss, and has shorter operative time and skin scar.