Qiming Fan

Renji Hospital, Shanghai, Shanghai Shi, China

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Publications (11)55.8 Total impact

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    ABSTRACT: Wear-particle-induced osteolysis leads to prosthesis loosening, which is one of the most common causes of joint-implant failure, a problem that must be fixed using revision surgery. Thus, a potential treatment for prosthetic loosening is focused on inhibiting osteoclastic bone resorption, which prevents wear-particle-induced osteolysis. In this study, we synthesized a compound named OA-14 (N-(3- (dodecylcarbamoyl)phenyl)-1H-indole-2-carboxamide) and examined how OA-14 affects titanium (Ti)-particle-induced osteolysis and osteoclastogenesis. We report that OA-14 treatment protected against Ti-particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of tartrate-resistant acid phosphatase-positive osteoclasts decreased after treatment with OA-14 in vivo, which suggested that OA-14 inhibits osteoclast formation. To test this hypothesis, we conducted in vitro studies, and our results revealed that OA-14 markedly diminished osteoclast differentiation and osteoclast-specific gene expression in a dose- and time-dependent manner. Moreover, OA-14 suppressed osteoclastic bone resorption and F-actin ring formation. Furthermore, we determined that OA-14 inhibited osteoclastogenesis by specifically blocking the p38-Mitf-c-fos-NFATc1 signaling cascade induced by RANKL (ligand of receptor activator of nuclear factor κB). Collectively, our results suggest that the compound OA-14 can be safely used for treating particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.
    Biomaterials 07/2014; · 8.31 Impact Factor
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    ABSTRACT: Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure.
    Experimental cell research. 07/2014;
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    ABSTRACT: Recent studies on bone have shown an endocrine role of the skeleton, which could be impaired in various human diseases, including osteoporosis, obesity, and diabetes-associated bone diseases. As a sensor and regulator of energy metabolism, AMP-activated protein kinase (AMPK) may also play an important role in the regulation of bone metabolism. The current study aimed to establish the expression profiles and phosphorylation patterns of AMPK subunits in several mesenchymal cell types.
    Chinese medical journal. 07/2014; 127(13):2451-7.
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    ABSTRACT: The aim of this study was to assess the effect of enoxacin on osteoclastogenesis and titanium particle-induced osteolysis. Wear particles liberated from the surface of prostheses are associated with aseptic prosthetic loosening. It is well established that wear particles induce inflammation, and that extensive osteoclastogenesis plays a critical role in peri-implant osteolysis and subsequent prosthetic loosening. Therefore, inhibiting extensive osteoclast formation and bone resorption could be a potential therapeutic target to prevent prosthetic loosening. In this study, we demonstrated that enoxacin, a fluoroquinolone antibiotic, exerts potent inhibitory effects on titanium particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of mature osteoclasts decreased after treatment with enoxacin in vivo, suggesting that osteoclast formation might be inhibited by enoxacin. We then performed in vitro studies to confirm our hypothesis and revealed the mechanism of action of enoxacin. Enoxacin inhibited osteoclast formation by specifically abrogating RANKL-induced JNK signaling. Collectively, these results suggest that enoxacin, an antibiotic with few side effects that is widely used in clinics, had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.
    Biomaterials 01/2014; 35(22):5721–5730. · 8.31 Impact Factor
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    ABSTRACT: Wear particle-induced aseptic prosthetic loosening is one of the most common reasons for total joint arthroplasty (TJA). Extensive bone destruction (osteolysis) by osteoclasts plays an important role in wear particle-induced peri-implant loosening. Thus, strategies for inhibiting osteoclast function may have therapeutic benefit for prosthetic loosening. Here, we mimicked the process of magnesium (Mg) degradation in vivo and obtained Mg leach liquor (MLL) by immersing pure Mg in culture medium. For the first time, we demonstrated that MLL suppresses osteoclast formation, polarization, and osteoclast bone resorption in vitro. An in vivo assay demonstrated that MLL attenuates wear particle-induced osteolysis. Furthermore, we found that MLL significantly inhibits nuclear factor-κB (NF-κB) activation by retarding inhibitor-κB degradation and subsequent NF-κB nuclear translocation. We also found that MLL attenuates the expression of NFATc1 at both the protein and mRNA levels. These results demonstrate that MLL has anti-osteoclast activity in vitro and prevents wear particle-induced osteolysis in vivo. Collectively, our study suggests that metallic magnesium, one of the orthopedic implants with superior properties, has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and function.
    Biomaterials 01/2014; 35(24):6299–6310. · 8.31 Impact Factor
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    ABSTRACT: Osteosarcoma is the most common primary malignancy of bone in adolescents and young adults. There is a shortage of tumorigenic and highly metastatic human osteosarcoma cell lines that can be used for metastasis study. Here we establish and characterize a highly metastatic human osteosarcoma cell line that is derived from Saos2 cell line based on bioluminescence. The occasional pulmonary metastatic cells developed from Saos2 were isolated, harvested, characterized and named Saos2-l. The parental Saos2 and Saos2-l cells were further characterized both in vitro and in vivo. Results showed that Saos2-l cells demonstrated increased cell adhesion, migration and invasion compared to the parental Saos2 cells. Conversely, Saos2-l cells grew at a slightly slower rate than that of the parental cells. When injected into nude mice, Saos2-l cells had a greater increase in developing pulmonary metastases compared to the parental Saos2 cells. Further transcriptional profiling analysis revealed that some gene expression were up-regulated or down-regulated in the highly metastatic Saos2-l cells, indicating possible influencing factors of metastasis. Thus, we have established and characterized a highly metastatic human osteosarcoma cell line that should serve as a valuable tool for future investigations on the pathogenesis, metastasis and potential treatments of human osteosarcoma.
    International journal of clinical and experimental pathology. 01/2014; 7(6):2871-82.
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    ABSTRACT: Bone is a major site of metastasis for several types of malignant tumor. Specific interactions between tumor cells and the bone microenvironment contribute to the tendency of tumors to metastasize to bone. Furthermore, Wnt5a participates in the progression of several types of malignant tumor. This study investigates the role of Wnt5a in the migration of the prostate cancer (PCa) cell line PC3 toward bone marrow stromal cell (BMSC)‑conditioned medium (CM). The expression of 22 genes associated with bone metastasis was measured in three PCa cell lines (LNCaP, PC3 and DU145). Subsequently, the proliferation and migration capacities of PC3 cells treated either with small interfering RNA (siRNA) against Wnt5a or with recombinant mouse (rm) Wnt5a were analyzed with alamarBlue and transwell assays. BMSC‑CM was collected to evaluate its effect on PC3 cell migration. Also, the expression of Wnt5a in BMSCs was knocked down prior to collection of the CM to evaluate its effects on the migration of PC3 cells. Significantly higher levels of Wnt5a mRNA expression were identified in the PC3 cells, compared with those in LNCaP and DU145 cells. Silencing Wnt5a expression with siRNA reduced the migration capacity of PC3 cells by 50%. The addition of rmWnt5a improved the migration capacity of PC3 cells in a concentration‑dependent manner. PC3 cells preferred to migrate toward BMSC‑CM than toward the control. CM from Wnt5a siRNA‑treated BMSCs significantly reduced PC3 cell migration. Wnt5a promotes PC3 cell migration toward BMSC‑CM, indicating that Wnt5a is a potential therapeutic target for the treatment of advanced PCa.
    Molecular Medicine Reports 09/2013; · 1.17 Impact Factor
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    ABSTRACT: Bone defects are common in elderly patients suffering from osteoporosis. Current methods of bone defect treatment for osteoporosis are not always satisfactory. In this study, we demonstrated that bone marrow mesenchymal stem cells (MSCs) harvested from goats with long-term estrogen deficiencies exhibited a lower proliferation rate and decreased osteogenic capacity, which are critical obstacles for bone defect repair in the elderly. However, by combining autologous enriched bone marrow mesenchymal stem cells with porous β-TCP, we successfully repaired critical-sized bone defects in the medial femoral condyle of the osteoporotic goats. Both micro-CT images and histomorphometry analysis illustrated improved bone formation following the enriched MSC therapy. Thus, we proposed autologous enriched bone marrow mesenchymal stem cells as a quick, safe therapeutic strategy to treat osteoporotic bone defects.
    Biomaterials 04/2012; 33(20):5076-84. · 8.31 Impact Factor
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    ABSTRACT: Although Sox9 is essential for chondrogenic differentiation and matrix production, its application in cartilage tissue engineering has been rarely reported. In this study, the chondrogenic effect of Sox9 on bone marrow mesenchymal stem cells (BMSCs) in vitro and its application in articular cartilage repair in vivo were evaluated. Rabbit BMSCs were transduced with adenoviral vector containing Sox9. Toluidine blue, safranin O staining and real-time PCR were performed to check chondrogenic differentiation. The results showed that Sox9 could induce chondrogenesis of BMSCs both in monolayer and on PGA scaffold effectively. The rabbit model with full-thickness cartilage defects was established and then repaired by PGA scaffold and rabbit BMSCs with or without Sox9 transduction. HE, safranin O staining and immunohistochemistry were used to assess the repair of defects by the complex. Better repair, including more newly-formed cartilage tissue and hyaline cartilage-specific extracellular matrix and greater expression of several chondrogenesis marker genes were observed in PGA scaffold and BMSCs with Sox9 transduction, compared to that without transduction. Our findings defined the important role of Sox9 in the repair of cartilage defects in vivo and provided evidence that Sox9 had the potential and advantage in the application of tissue engineering.
    Biomaterials 03/2011; 32(16):3910-20. · 8.31 Impact Factor
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    ABSTRACT: Bone-like fluoridated hydroxyapatite (FHA) coatings were prepared on Mg-6 wt.%Zn substrates using electrochemical method. Human bone marrow stromal cells (hBMSCs) were utilized to investigate the cellular biocompatibility of Mg-6 wt.%Zn alloy after surface modification. The adhesion of hBMSCs was evaluated using scanning electron microscopy (SEM) and laser scanning confocal microscopy (LSCM). The proliferation of the cells was also measured by carrying out the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. And the alkaline phosphatase activity (ALP) was assessed to evaluate the early stage of differentiation. Lastly, reverse transcription-polymerase chain reaction (RT-PCR) test was taken. It was found that the hBMSCs displayed better cell functions on the bioactive FHA coated alloy, compared to the bare Mg-6 wt.%Zn alloy. The in vitro results indicated that the bioactive FHA coating can improve the interfacial bioactivity of Mg-6 wt.%Zn substrate, specifically, both on biodegradation behavior control and good cellular proliferation and differentiation.
    Biomaterials 08/2010; 31(22):5782-8. · 8.31 Impact Factor
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    ABSTRACT: The balance between osteogenesis and adipogenesis of mesenchymal stem cells is disrupted in various human diseases. Investigating the mechanisms that fine-tune this balance is of medical importance. Identification of potential target gene which can be used to study the relationship between them could be really helpful for this purpose. In the current study, we used C3H10T1/2 as model cells and through which two models of both osteogenesis induced by bone-morphogenetic protein (BMP)-2 and transdifferentiation from osteogenesis to adipogenesis were established. We investigated the role of CCAAT/enhancer binding protein (C/EBP)-alpha in these two systems. Then from epigenetic point of view, we elucidated the underlying molecular mechanisms preliminarily. The results showed that down-regulations of both C/EBP-alpha expression and its inducibility in response to insulin, fetal bovine serum, methylisobutylxanthine and dexamethasone (IFMD) adipogenic hormonal cocktail were observed in terminal stage of osteogenesis of C3H10T1/2 cells induced by BMP-2. And overexpression of C/EBP-alpha could lead to inhibition of osteogenesis differentiation and rescue attenuation of potential of adipogenic conversion in this process. Furthermore, we provided evidence that remarkable DNA hypermethylation and histones 3 and 4 hypoacetylation in -1286 bp/1065 bp promoter region of C/EBP-alpha were involved in both of down-regulations. Our data suggest that C/EBP-alpha functions as regulator in the balance between osteogenesis and adipogenesis of C3H10T1/2 cells and may be a therapeutic target.
    Journal of Cellular and Molecular Medicine 01/2009; 13(8B):2489-505. · 4.75 Impact Factor

Publication Stats

52 Citations
55.80 Total Impact Points

Institutions

  • 2013–2014
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2010–2014
    • Shanghai Jiao Tong University
      • • Department of Orthopaedics
      • • School of Materials Science and Engineering
      Shanghai, Shanghai Shi, China
  • 2009
    • Shanghai Institutes for Biological Sciences
      • Institute of Health Sciences
      Shanghai, Shanghai Shi, China