Zhengang Zha

Acceleration of wound healing in traumatic ulcers by absorbable collagen sponge containing recombinant basic fibroblast growth factor

The objective of this study was to examine the safety and efficacy of topical application of recombinant basic fibroblast growth factor loaded on a kind of absorbable collagen sponge (rbFGF/ACS) in patients with chronic traumatic ulcers. This double-blind controlled trial included 58 patients with chronic traumatic ulcers. The patients were randomized into two groups. After debridement, the wounds were covered with rbFGF/ACS and then bound up with sterile gauze in the rbFGF/ACS group (n = 30), or bound up with petrolatum sterile gauze in the placebo group (n = 28). The complete closure of the wounds was assessed by photography. The wounds that failed to heal were defined as incomplete healing after 3 weeks. Compared with the placebo group, rbFGF/ACS significantly increased the incidence of complete wound closure by 68% (90.0% versus 53.6%, P = 0.0019) after 3 weeks and shortened the time to achieve complete wound closure by 24% (10.6 days versus 13.9 days, P = 0.0171). There was no difference in side effects between the two groups. rbFGF/ACS significantly increased the incidence of complete wound closure, shortened the complete healing time and improved the healing quality of chronic traumatic ulcers. The safety profile in the rbFGF/ACS group was similar to that in placebo group.

MicroRNA-9 regulates the development of knee osteoarthritis through the NF-kappaB1 pathway in chondrocytes.

AbstractIt has been suggested that microRNA-9 (miR-9) is associated with the development of knee osteoarthritis (OA). This study was aimed to investigate the association between the mechanism of miR-9 targeting nuclear factor kappa-B1 (NF-&kgr;B1) and the proliferation and apoptosis of knee OA chondrocytes.Cartilage samples were collected from 25 patients with knee OA and 10 traumatic amputees, and another 15 OA rat models, together with 15 rats without knee OA lesions were also established. MiR-9 expressions in both knee OA cartilage and normal cartilage samples were detected using quantitative real-time PCR. The expressions of related genes (NF-&kgr;B1, IL-6, and MMP-13) in the two groups were also detected. Dual luciferase reporter gene assay was employed to examine the effect of miR-9 on the luciferase activity of NF-&kgr;B1 3′UTR. Knee OA chondrocytes were transfected with miR-9 mimics, miR-9 inhibitor, and NF-&kgr;B1 siRNA, respectively, and changes in cellular proliferation and apoptosis were detected via MTT assay and flow cytometric analysis, respectively. Western blotting assay was used to detect the expressions of NF-&kgr;B1, interleukin-6 (IL-6), and matrix metalloproteinase-13 (MMP-13).According to results from human OA samples and rat OA models, miR-9 was significantly downregulated in knee OA cartilage tissues compared with normal cartilage tissues (P < 0.01). The expressions of NF-&kgr;B1, IL-6, and MMP-13 in knee OA cartilage tissues were significantly higher than those in normal cartilage tissues (P < 0.01). Dual luciferase reporter gene assay showed that miR-9 could bind to the 3′UTR of NF-&kgr;B1 and significantly inhibit the luciferase activity by 37% (P < 0.01). Upregulation of miR-9 or downregulation of NF-&kgr;B1 could promote cell proliferation and suppress cell apoptosis.Conclusively, downregulated miR-9 can facilitate proliferation and antiapoptosis of knee OA chondrocytes by directly binding to NF-kB1, implying that stimulating miR-9 expressions might assist in treatment of knee OA.

Morphology and mechanics of chondroid cells from human adipose-derived Stem cells detected by atomic force microscopy

Chondroid cell from human adipose-derived stem cells (ADSCs) has emerged as an alternative treatment option for articular cartilage defects. Herein, we successfully compared ADSCs, normal chondrocytes, and chondroid cells. The comparative study of ADSCs and chondroid cells revealed type II collagen (COL II) and glycosaminoglycans expression of chondroid cells were similar to those in normal chondrocytes, and much higher than ADSCs. Using atomic force microscope (AFM) and laser confocal scanning microscopy (LCSM), we compared the differences in morphology, mechanical properties, and F-actin distribution between chondroid cells and normal chondrocytes. Our results showed no differences observed between these two types of cells regarding morphology, stiffness, and F-actin distribution. However, found that the adhesion force in chondroid cells was lower than that in normal chondrocytes. Taken together, our AFM and LCSM analyses suggest that the lower adhesion force in chondroid cells may contribute to the dedifferentiation of ADSC-derived chondroid cells. Future examination of surface adhesion force-related protein expression will likely provide new insight into the molecular mechanisms underlying the dedifferentiation of ADSC-derived chondroid cells.

Metabolic Syndrome Increases the Risk for Knee Osteoarthritis: A Meta-Analysis.

Background. Studies revealed that metabolic factors might contribute substantially to osteoarthritis (OA) pathogenesis. There has been an increasing interest to understand the relationship between knee OA and the metabolic syndrome (MetS). The purpose of this study was to explore the association between metabolic syndrome and knee osteoarthritis using meta-analysis. Methods. Databases, including PUBMED, EMBASE, and the Cochrane Library, were searched to get relevant studies. Data were extracted separately by two authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results. The meta-analysis was finished with 8 studies with a total of 3202 cases and 20968 controls finally retrieved from the database search. The crude pooled OR is 2.24 (95% CI = 1.38–3.64). Although there was significant heterogeneity among these studies, which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study. The pooled adjusted OR remained significant with pooled adjusted OR 1.05 (95% CI = 1.03–1.07, p < 0.00001). No publication bias was found in the present meta-analysis. Conclusions. The synthesis of available evidence supports that metabolic syndrome increases the risk for knee osteoarthritis, even after adjustment for many risk factors.

The roles of integrin β1 in phenotypic maintenance and dedifferentiation in chondroid cells differentiated from human adipose-derived stem cells

ObjectiveThe aim of this study is to probe the intrinsic mechanism of chondroid cell dedifferentiation in order to provide a feasible solution for this in cell culture.MethodsMorphological and biomechanical properties of cells undergoing chondrogenic differentiation from human adipose-derived stem cells (ADSCs) were measured at the nanometer scale using atomic force microscopy and laser confocal scanning microscopy. Gene expression was determined by real-time quantitative polymerase chain reaction.ResultsThe expression of COL II, SOX9, and Aggrecan mRNA began to increase gradually at the beginning of differentiation and reach a peak similar to that of normal chondrocytes on the 12th day, then dropped to the level of the 6th day at 18th day. Cell topography and mechanics trended resembled those of the genes’ expression. Integrin β1 was expressed in ADSCs and rapidly upregulated during differentiation but downregulated after reaching maturity.ConclusionsThe amount and distribution of integrin β1 may play a critical role in mediating both chondroid cell maturity and dedifferentiation. Integrin β1 is a possible new marker and target for phenotypic maintenance in chondroid cells.

Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis

Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti‐cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro‐induced G2/M cell cycle arrest of chondrosarcoma by fine‐tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor‐differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose‐dependently down‐regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF‐1) mRNA expression and an enhancement of TCF‐1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of β‐catenin were not altered upon the treatment of Andro, suggesting that β‐catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF‐1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF‐1/SOX9 axis. J. Cell. Biochem. 118: 4575–4586, 2017.

Changes in coagulation functions and hemorheological parameters may predict hematoma formation after total knee arthroplasty

BackgroundHematoma formation around the knee is commonly seen after total knee arthroplasty (TKA) and may cause patient discomfort and worry regarding the success of the surgery. This study aimed to evaluate the coagulation functions and hemorheological parameters in patients undergoing TKA and investigate their associations with hematoma formation.MethodsThis study prospectively included 146 patients treated for knee osteoarthritis by unilateral TKA between August 2013 and August 2014. Apixaban was administered twice during the 12–24-h period after surgery. Blood coagulation functions were evaluated according to activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time, and fibrinogen preoperatively and on postoperative days 1, 3, 7, and 14. Hemorheological parameters were also measured. Patients were divided into a hematoma group and a non-hematoma group for comparison.ResultsOn postoperative day 1, the hematoma group showed significantly prolonged APTT and PT and significantly decreased hematocrit relative to baseline values (P < 0.05). The whole blood high shear rate, whole blood low shear rate, plasma viscosity, and hematocrit did not differ significantly between the two groups at baseline or from postoperative days 1–14 in (P > 0.05).ConclusionsProlonged APTT and PT on the first day after TKA as well as decreased hematocrit may indicate an increased risk of hematoma formation. Postoperative use of apixaban may promote the formation of ecchymoses but is not a major contributing factor.

Classification and Morphological Parameters of the Scapular Spine: Implications for Surgery.

AbstractIncidence of scapular spine (SS) fractures as a result of complications of reverse total shoulder arthroplasty is relatively high leading to inferior clinical outcomes and an increased risk of revision and dislocation. Fractures of SS because of trauma, including the acromion, constitute 6% to 23% of scapula fractures. The purpose of this study was to classify the SS and present specific geometrical parameters according to osteologic features. A total of 319 intact dry scapulae were collected and classified based on morphological characteristics and shape of the SS. Nine bony landmarks were also chosen and described for their relevance to regions of interest for scapular fixation. Five specific types of SS were noted and the most prevalent groups were Type 1 (Fusiform shape) (47.17%) and Type 5 (Horizontal S-shape) (19.18%). Overall, Types 3, 4, and 1 showed thicker landmark values compared to Type 5, with Type 2 having smaller values. Our classification into 5 distinct types allowed appreciation of the anatomical variance of SSs. The contours of Types 5 and 1 presented a more complex morphology and may lead to a worse surgical approach due to a fracture. As Types 2 and 5 were much thinner than the other types, these may be more susceptible to fractures.

Expression and Significance of MMPs in Synovial Fluid, Serum and PBMC Culture Supernatant Stimulated by LPS in Osteoarthritis Patients With or Without Diabetes

OBJECTIVE Patients with Type 2 Diabetes mellitus (T2DM) are prone to osteoarthritis (OA). Matrix metalloproteinases (MMPs), an essential modulator in cartilage matrix homeostasis, increase in T2DM and OA. We aimed to ascertain the expression difference of MMPs and function in mononuclear cells after stimulating by lipopolysaccharide (LPS) in OA patients with or without diabetes. METHODS 30 knee OA patients without T2DM (OA group), 20 knee OA patients with T2DM (DM-OA group) and 5 healthy volunteers recruited as control were enrolled from January 2016 to January 2017. The expression levels of MMPs in both serum and synovial fluid were initially detected in three groups by enzyme-linked immunosorbent assay (ELISA). After stimulation of peripheral blood mononuclear cell (PBMC) with LPS, the release of MMPs were determined and evaluated. RESULTS The expression of MMP-1, -7, -8, -9, -10 and -12 in synovial fluid in DM-OA group were significantly higher than in OA group and healthy control. The expression of MMP-1 and -7 in serum were highest in DM-OA group. LPS significantly promotes the production of MMP-1, -8, -9 and -10 in PBMC of each group after 4 h stimulation. It is worth to note that the LPS-stimulated MMP-8 and -9 elevations were more prominent in DM-OA group compared with their counterparts. CONCLUSION High levels of MMP-1, -7, -8, -9, -10, and -12 in the synovial fluid might be one of important reasons that diabetes patients are more frequently suffered from OA. Inflammation-induced malfunction of mononuclear cells would stimulate MMP-8 and -9 secretion to various extents.