Decreased synovial fluid pituitary adenylate cyclase-activating polypeptide (PACAP) levels may reflect disease severity in post-traumatic knee osteoarthritis after anterior cruciate ligament injury.

BACKGROUND: It has been demonstrated that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic knee osteoarthritis (PTKOA).Pituitary adenylate cyclase-activating polypeptide (PACAP), a common neuropeptide exerting a wide spectrum of functions, has been proved to inhibit inflammation and prevent cartilage degeneration. OBJECTIVE: The current study was performed to investigate circulating and synovial fluid PACAP concentrations in ACL injury patients to determine their relationship with the disease progression of the severity of post-traumatic knee osteoarthritis (PTKOA). METHODS: 72 ACL injury patients receiving arthroscopical examination and surgery were enrolled in the study. Meanwhile, 60 gender-and-age non-traumatic patellar dislocation patients were enrolled as controls. The VAS score, Lysholm Score and International Knee Documentation Committee (IKDC) score were all recorded to evaluate the clinical severity. Serum and synovial fluid (SF) PACAP levels were investigated by enzyme-linked immunosorbent assay (ELISA).The IL-1ß and TNF-α levels were also investigated. The degree of meniscus injury was assessed by MR imaging. The modified Mankin score was recorded to examine the cartilage histopathological alternations. Receiver operating characteristic (ROC) curve was performed to discuss the diagnostic value of PACAP levels for the prediction of the radiographic grading in comparison with IL-1ß and TNF-α. RESULTS: Serum PACAP levels between PTKOA patients and patellar dislocation did not reach significant differences. However, SF PACAP levels were significantly lower in PTKOA patients than controls. In addition, SF PACAP levels were negatively associated with MRI imaging grade for meniscus injury and VAS score, and were positively associated with Lysholm and IKDC scores. In addition, SF PACAP levels were negatively related to Mankin score as well as the expressions of IL-1ß and TNF-α. ROC analysis curve showed that attenuated PACAP may serve as a favorable marker for the diagnosis of MRI for meniscus injury. CONCLUSIONS: SF PACAP concentrations showed an independent and negative association with disease severity in PTKOA following ACL injury. Local treatment with PACAP may act as a possible adjuvant therapy for delaying the process of PTKOA.

The synovial fluid neuropeptide PACAP may act as a protective factor during disease progression of primary knee osteoarthritis and is increased following hyaluronic acid injection.

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-1ß 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-1ß, 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-1ß 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.

Role of TGF­ß1 expressed in bone marrow­derived mesenchymal stem cells in promoting bone formation in a rabbit femoral defect model.

Bone defects represent a major clinical and socioeconomic problem without suitable treatment options. Previous studies have shown that transforming growth factor ß1 (TGF­ß1) is important in the development of various diseases. The present study aimed to investigate the therapeutic potential of rabbit bone marrow­derived mesenchymal stem cells (BMSCs) expressing TGF­ß1 in the treatment of rabbit femoral defects. First, rabbit BMSCs were identified and cultured. TGF­ß1 was then stably overexpressed in the rabbit BMSCs by lentivirus transfection, which was expressed at a high level in the femoral defects treated with TGF­ß1­overexpressing BMSCs, compared with PBS­treated controls. In addition, the TGF­ß1­overexpressing BMSCs promoted new bone formation in the rabbit femoral defect model, and increased the expression of bone­related markers at week 2 and week 6. Therefore, the study demonstrated that BMSCs overexpressing TGF­ß1 may provide a novel therapeutic option for femoral defects.