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The correlation of serum and synovial fluid (SF) pituitary adenylate cyclase-activating polypeptide (PACAP) levels with disease progression of primary knee osteoarthritis (OA) was explored. Radiographic severity of OA was determined by Kellgren–Lawrence (K-L) grades. PACAP levels were measured by ELISA before treatment, and 4 and 8 wk following hyaluronic acid (HA) injection. Levels of IL-1β and MMP-3 were also detected. The numeric pain scale (NPS), revised Oxford Knee Score (OKS), and American Knee Society Score (AKSS) were employed to evaluate to symptomatic severity. Receiver-operating-characteristic (ROC) curve analysis was carried out to compare the diagnostic value of PACAP, IL-1β, and MMP-3 for the K-L grade. PACAP concentrations in SF but not serum were significantly lower in OA patients compared with controls. SF PACAP levels were negatively associated with K-L grades and higher NPS as well as worse AKSS and OKS. Further analysis demonstrated that PACAP concentration in SF was negatively correlated with expressions of IL-1β as well as MMP-3 and may act as a marker for radiographic progression along with MMP-3. Last, we found SF PACAP levels exhibited an incremental trend after HA injection. These findings confirmed the crucial role of PACAP deficiency in the development of primary knee OA.

Bone defects represent a major clinical and socioeconomic problem without suitable treatment options. Previous studies have shown that transforming growth factor β1 (TGF-β1) is important in the development of various diseases. The present study aimed to investigate the therapeutic potential of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) expressing TGF-β1 in the treatment of rabbit femoral defects. First, rabbit BMSCs were identified and cultured. TGF-β1 was then stably overexpressed in the rabbit BMSCs by lentivirus transfection, which was expressed at a high level in the femoral defects treated with TGF-β1-overexpressing BMSCs, compared with PBS-treated controls. In addition, the TGF-β1-overexpressing BMSCs promoted new bone formation in the rabbit femoral defect model, and increased the expression of bone-related markers at week 2 and week 6. Therefore, the study demonstrated that BMSCs overexpressing TGF-β1 may provide a novel therapeutic option for femoral defects.

Increased expression of p53 and p73 in esophageal carcinoma may serve as an indicator of tumor severity. Detection of these proteins in future studies may help understand the mechanisms of development, invasion and metastasis in esophageal cancer.

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