Smad4 is the common mediator of transforming growth factor-B (TGF-B) superfamily signaling, which functions in diverse developmental processes in mammals. To study the role of Smad4 in skin development, a keratinocyte-specific null mutant of Smad4 (Smad4 co/co ;K5-Cre) was generated in mice using the Cre-loxP system. The Smad4-mutant mice exhibited progressive alopecia as a result of the mutant hair follicles failing to undergo programmed regression. Sonic hedgehog (Shh) was only detected in Smad4-mutant hair follicles at the catagen stage. Seventy percent of Smad4 co/co ; K5-Cre mice developed spontaneous tumors within 12 months of birth. c-Myc and cyclin D1 were up-regulated whereas p21 and p27 expressions were decreased, which correlated with the epidermal hyperplasia in Smad4 mutants. Interestingly, coordinated deletion of the Smad4 and PTEN genes resulted in accelerated hair loss and skin tumor formation, suggesting that Smad4 and PTEN act synergistically to regulate epidermal proliferation and differentiation. All of our data indicate that Smad4 is essential for catagen induction and acts as a critical suppressor in skin tumorigenesis. (Cancer Res 2005; 65(19): 8671-8)

Cartilage-derived mesenchymal stem cells (MSCs) have been isolated with different methods. In this study lateral and medial femoral condyles were respectively collected from patients with late-stage osteoarthritis during the total knee arthroplasty. After digestion of the cartilage tissues with type II collagenase and analysis by fluorescence-activated cell sorting (FACS) with CD146, a chondroprogenitor cell sub-population were isolated and purified. The expression of other MSC-associated markers in the CD146 þ chondroprogenitors was analyzed by flow cytometry. Multi-lineage differentiation capacity of CD146 þ chondroprogenitors was compared with that of unsorted chondrocytes and adipose-derived MSCs (ADMSCs). Higher percentage of CD146 þ chondroprogenitors isolated from the medial femoral condyles was observed than that from the lateral. CD146 þ chondroprogenitors expressed high levels of MSC-specific surface antigens, and showed higher chondrogenesis capacity than ADMSCs and unsorted chondrocytes in a 3D cell pellet culture model. Thus CD146 might be a new cell surface marker for cartilage progenitor cell population in the late-stage osteoarthritis.

BackgroundLimited studies are available to investigate the prevalence of preoperative venous thromboembolism (VTE) in elderly patients with femoral neck fractures. Our primary aim was to determine the incidences of VTE and its risk or protective factors in such patient population. The secondary objective was to evaluate the need of therapeutic anticoagulation for isolated calf muscular venous thrombosis (ICMVT) prior to femoral neck fracture surgery.MethodsThis is a retrospective case-control study, including 301 femoral neck fracture patients who were admitted to our institution between January 2014 and March 2017. Bilateral Doppler ultrasonography was performed in each of the patients as a preoperative VTE screening. The event rate of VTE was calculated, and significant risk or protective factors were determined by using a multivariate logistic regression model. Patients with ICMVT were divided into anticoagulation and no anticoagulation groups to assess the efficacy and safety of preoperative therapeutic anticoagulation. Intraoperative blood loss, drainage volume, blood transfusion, perioperative hemoglobin change, and rate of thrombosis extension were compared between the two groups.ResultsThe overall preoperative incidence of VTE in patients with femoral neck fracture was 18.9% (57/301), in which deep vein thrombosis (DVT) was 18.9% and pulmonary embolism (PE) was 1%. Among the DVT cases, 77.2% (44/57) were ICMVTs. Multiple fractures (odds ratio [OR] = 9.418; 95% confidence interval [CI] = 2.537 to 34.96), coexisting movement disorder (OR = 3.862; 95% CI = 1.658 to 8.993), bed rest for more than 7 days (OR = 2.082; 95% CI = 1.011 to 4.284) as well as elevated levels of D-dimer (OR = 1.019; 95% CI = 1.002 to 1.037) and fibrinogen (OR = 1.345; 95% CI = 1.008 to 1.796) led to an increase in the risk of VTE, while the recent use of antiplatelet drug (OR = 0.424; 95% CI = 0.181 to 0.995) and prophylactic anticoagulation (OR = 0.503; 95% CI = 0.263 to 0.959) decreased the risk of VTE. For the 39 patients with ICMVT undergoing femoral neck fracture surgery, there were no significant differences in the rate of thrombosis extension between anticoagulation and no anticoagulation groups, but significantly decreased postoperative hemoglobin was observed in the anticoagulation group.ConclusionOur findings showed a high prevalence of preoperative VTE in elderly patients with femoral neck fracture, with risk factors identified. We found that the most detected VTE were ICMVTs. Our study suggested that a direct surgery without preoperative use of therapeutic anticoagulation for ICMVT would not reduce the risk of thrombus extension, and the therapeutic use of anticoagulation may worsen postoperative anemia.