Effects of platelet-derived growth factor on chondrocyte proliferation, migration and apoptosis via regulation of GIT1 expression.

The formation of fibrocartilage, cartilaginous and bony calluses is vital for bone healing following a fracture. Fibroblasts, chondrocytes and osteoblasts are critical functional cells that are involved in these three processes, respectively. Platelet­derived growth factor (PDGF), a growth factor that is released from platelet particles and appears during the early stages at the site of fractures, is essential in bone healing via regulation of cell proliferation and differentiation. However, the effects of PDGF on the chondrocytes remain unclear. In the present study, PDGF promoted phosphorylation of Src and upregulated the expression level of G­protein­coupled receptor kinase interacting protein­1 (GIT1) according to the results of the cell culture of chondrocytes in vitro and western blotting. However, the effect of PDGF on the upregulation of GIT1 expression was mostly inhibited by the Src inhibitor, PP2. After knocking down GIT1 expression using siRNA, the phosphorylation of Src continued to be induced by PDGF, although the expression of GIT1 was inhibited. Furthermore, the results indicated that PDGF promoted chondrocyte proliferation and migration, however, the effect on cell apoptosis induction was suppressed after adding the Src inhibitor, PP2. Additionally, when knocking down GIT1 using siRNA, the expression level of GIT1 decreased, which is similar to the effect of the Src inhibitor, PP2. The current study demonstrates that PDGF may initially activate the phosphorylation of Src, and subsequently induce GIT1 expression to promote chondrocyte proliferation and migration, but suppress cell apoptosis.

Lentivirus-mediated RNA interference targeting UbcH10 reduces cell growth and invasion of human osteosarcoma cells via inhibition of Ki-67 and matrix metalloproteinases.

Osteosarcoma (OS) is the most commonly diagnosed primary malignancy affecting the bone. UbcH10 is a cancer-related E2-ubiquitin-conjugating enzyme. An overexpression of UbcH10 is significantly associated with tumor grade and cellular proliferation. However, limited evidence exists with regard to the biological function of UbcH10 in OS. The present study created a UbcH10 knockdown OS cell line using lentivirus-mediated RNA interference. The expression of UbcH10 was significantly reduced in UbcH10-targeted small hairpin RNA-expressing lentivirus OS cells. The downregulation of UbcH10 suppressed OS cell proliferation and colony formation ability via decreased Ki-67 expression. UbcH10 knockdown OS cells exhibited impaired invasion and migration abilities. Furthermore, knockdown of UbcH10 led to decreased levels of matrix metalloproteinase-3 and -9 in OS cells. The present study demonstrated the role of UbcH10 in OS cell proliferation, invasion and migration, which suggests that UbcH10 may be a potential candidate for OS therapy.

Diagnostic potential of strain ratio measurement and a 5 point scoring method for detection of breast cancer: Chinese experience.

AIM: To evaluate the differential diagnostic potential of lesion stiffness assessed by the sonoelastographic strain index ratio (SR) and elastographic color scoring system (UE) for breast lesions. MATERIALS AND METHODS: Three hundred and forty two breast masses (158 benign and 184 malignant) from 325 consecutive patients (mean age 44.2 years; range 16-81)who had been scheduled for a sonographically guided core biopsy were examined with grey scale sonography,doppler sonography and sonoelastography. Each lesion was classified with ACR's BI-RADS assessment category (2, 3 and 4A=Benign and; 4B, 4C, 5=Malignant) and the 5-point scoring system proposed by Itoh et al, with scoring 1-3=benign and 4-5=malignant. Strain and area ratios of each lesion were calculated within the same machine. Histological diagnosis was used as the reference standard. The area under the curve (AUC) and cut-off point were obtained by receiver operating curve and the cross table Fischer Test was carried out for assessing diagnostic value. Sensitivity, specificity, PPV, NPV, accuracy and false-discovery rates were compared. RESULTS: The mean strain ratios for benign and malignant lesions were 1.87 and 7.9 respectively. (P<0.0001). When a cutoff point of 3.54 was used, SR had a sensitivity of 94.6%, a specificity 94.3%, a PPV of 95.1%, an NPV of 93.7% and an accuracy of 94.4%. The AUC values were 0.90 for the 5 point scoring system (UE) and 0.96 for the strain index ratio. The overall diagnostic performance was SR method was better (P<0.05). CONCLUSIONS: Strain ratio measurement could be another effective predictor in elastography imaging besides 5 the point scoring system for differential diagnosis of breast lesions.