Biomedical subjects

Feng-Sheng Wang

Publications and source records attributed to Feng-Sheng Wang.

At least 19 recordsLinked to original sources

PubMed2006

Knocking down dickkopf-1 alleviates estrogen deficiency induction of bone loss. A histomorphological study in ovariectomized rats.

Dickkopf-1 (DKK1) has been found to act as a potent Wnt signaling-inhibitory factor for regulating skeletal disorders. We investigated whether modulation of DKK1 expression by end-capped phosphorothioate DKK1 antisense oligonucleotide could alter estrogen loss-induced bone loss. Ovariectomized or sham-operated rats were given 20 microg/kg/day DKK1 sense or antisense oligonucleotide or vehicle for 28 days. Femurs and tibiae were dissected to assess bone mass, biomechanical strength, immunohistochemistry and ex vivo osteoclast formation. We found that DKK1 antisense oligonucleotide significantly abrogated the suppressing effect of ovariectomy on weight, mineral content, mineral density and peak load of femurs. DKK1 antisense oligonucleotide treatment reduced ovariectomy promotion of ex vivo osteoclast differentiation of primary M-CSF-dependent bone marrow macrophages. Histomorphometric observation demonstrated that DKK1 antisense oligonucleotide treatment increased osteoblast number and impaired ovariectomy-promoted trabecular bone loss and osteoclast number in bone tissue. Osteoblastic cells adjacent to endosteum of trabecular bone and chondrocytes at calcified cartilage expressed intensive DKK1 and RANKL and weak OPG immunostaining in ovariectomized rat bone microenvironments. Osteogenic cells and chondral cells displayed weak DKK1, RANKL and OPG expression of bone tissue after DKK1 antisense oligonucleotide treatment. Taken together, attenuation of DKK1 expression in ovariectomized rat bone tissue alleviated loss of bone mass and biomechanical property. The regulatory action of DKK1 antisense oligonucleotide treatment on bone tissue appeared to suppress the promoting effect of estrogen deficiency on osteoclastogenesis-stimulatory factor RANKL expression and osteoclast differentiation. Control of DKK1 signaling can be used in the future as an alternative strategy for protecting estrogen deficiency induction of bone loss.

Animals↗

PubMed2006

Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells.

Glomerulosclerosis and diabetic nephropathy are attributable to high glucose induction of mesangial cell apoptosis. Whereas Wnt signaling has been found to regulate renal morphogenesis and pathogenesis, the biologic role of Wnt/beta-catenin signaling in controlling high glucose-induced mesangial cell apoptosis is not well defined. Herein is reported that Wnt/beta-catenin signaling is required for protecting glomerular mesangial cells from high glucose-mediated cell apoptosis. High glucose downregulated Wnt4 and Wnt5a expression and the subsequent nuclear translocation of beta-catenin, whereas it increased glycogen synthase kinase-3beta (GSK-3beta) and caspase-3 activities and apoptosis of glomerular mesangial cells. Suppression of GSK-3beta activation or increase in nuclear beta-catenin by transfection of Wnt4 or Wnt5a or stable beta-catenin (S33Y) reversed Akt activation and reduced the high glucose-mediated caspase-3 cleavage and cell apoptosis. Pharmacologic inhibition of GSK-3beta by recombinant Wnt5a or bromoindirubin-3'-oxime or LiCl increased Akt phosphorylation and beta-catenin translocation and abrogated high glucose-mediated proapoptotic activities. Exogenous bromoindirubin-3'-oxime treatment reduced phospho-Ser(9)-GSK-3beta and beta-catenin expression and apoptosis of cells adjacent to glomeruli in diabetic kidneys and attenuated urinary protein secretion in diabetic rats. Taken together, mesangial cells responded to high glucose by impairing that canonical Wnt pathway to increase proapoptotic activities. Sustaining Wnt/beta-catenin signaling is beneficial for promoting survival of mesangial cells that are exposed to high glucose stress.

Animals↗

PubMed2006

Extracorporeal shockwave treatment of osteonecrosis of the femoral head in systemic lupus erythematosis.

This article reported a case of systemic lupus erythematosis (SLE) with osteonecrosis of the femoral heads (ONFH-3) successfully treated with a novel extracorporeal shockwave treatment (ESWT). The follow-up at 3 years showed that both hips had no pain on activities for daily living. Magnetic resonance image (MRI) showed substantial reduction in bone marrow edema and no further collapse of the lesions. Radiographs and MRIs showed no change in the staging of the disease. ESWT provided beneficial effects for hips affected by ONFH in patients with SLE. This novel treatment modality resulted in significant pain relief and functional improvement of the hip and reduction in bone marrow edema in our patient. It appeared that ESWT might have the potential to curtail the progression of the disease and to delay the need for total hip arthroplasty in the very young patients contracted with SLE.

Adult↗

PubMed2006

Dexamethasone induction of keloid regression through effective suppression of VEGF expression and keloid fibroblast proliferation.

The biological mechanism underlying steroid therapy for treating keloids remains unclear. Analytical results demonstrated that topical intra-lesional steroid injections suppress vascular endothelial growth factor (VEGF) expression in keloid tissue and induce its regression in vivo. This study investigated whether glucocorticoid (dexamethasone) downregulates VEGF expression and hinders keloid fibroblast (KF) proliferation in keloid regression. Primary KF cultures were treated with various concentrations of dexamethasone, glucocorticoid receptor (GR) antagonist (mifeprostone, RU-486), VEGF-A antibody, VEGF receptor-2 (VEGF-R2) antagonist (SU-5416), and VEGF protein. Analytical results demonstrated that dexamethasone retarded KFs proliferation. However, suppression of fibroblast proliferation by dexamethasone pre-treatment was reduced by adding exogenous VEGF protein. Dexamethasone suppressed endogenous VEGF mRNA induction, protein expressed by KFs, and angiogenesis activity detected by a tube-forming assay of human umbilical vein endothelial cells co-cultured fibroblasts. These effects were reversed by pre-treatment with RU-486, and not by pre-treatment with SU-5416. Thus, dexamethasone induces keloid regression via interaction with the GR and suppresses endogenous VEGF expression and fibroblast proliferation. However, exogenous VEGF promotes fibroblast proliferation through the GR-independent pathway. Modulation of VEGF production may comprise a valuable treatment modality for keloids.

Antibodies, Monoclonal↗

PubMed2006

Long-term results of extracorporeal shockwave treatment for plantar fasciitis.

BACKGROUND: Extracorporeal shockwave treatment has shown mixed short-term results for plantar fasciitis. However, the long-term results are not available. HYPOTHESIS: Long-term results of shockwave treatment are comparable with short-term results. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: This prospective study consisted of 149 patients (168 heels) with an established diagnosis of chronic plantar fasciitis, including 79 patients (85 heels) in the shockwave treatment group and 70 patients (83 heels) in the control group. In the shockwave group, patients received 1500 impulses of shockwaves at 16 kV to the affected heel in a single session. Patients in the control group received conservative treatment consisting of nonsteroidal anti-inflammatory drugs, orthotics, physical therapy, an exercise program, and/or a local cortisone injection. Patients were evaluated at 60 to 72 months (shockwave group) or 34 to 64 months (control group) with a 100-point scoring system including 70 points for pain and 30 points for function. The clinical outcomes were rated as excellent, good, fair, or poor. RESULTS: Before treatment, the groups showed no significant differences in the scores for pain and function. After treatment, the shockwave group showed significantly better pain and function scores as compared with the control group. The overall results were 69.1% excellent, 13.6% good, 6.2% fair, and 11.1% poor for the shockwave group; and 0% excellent, 55% good, 36% fair, and 9% poor for the control group (P < .001). The recurrence rate was 11% (9/81 heels) for the shockwave group versus 55% (43/78 heels) for the control group (P < .001). There were no systemic or local complications or device-related problems. CONCLUSION: Extracorporeal shockwave treatment is effective and safe for patients with plantar fasciitis, with good long-term results.

Adult↗

PubMed2005

Correlation of augmented IL-8 production to premature chronic lung disease: implication of posttranscriptional regulation.

Despite that advances in neonatal medicine have significantly reduced the early mortality of premature infants, a considerable number of them are still prone to develop chronic lung disease (CLD) later. To find a method of early prevention, we investigated the efficacy of using certain early proinflammatory responses to predict the development of CLD. In the present study, 34 premature infants who required endotracheal intubation within 4 h of birth were recruited for analysis of IL-8, IL-10, and TNF-alpha levels in their bronchoalveolar lavage (BAL) fluid and blood. It was found that level of IL-8 but not TNF-alpha or IL-10 in initial BAL fluid was significantly correlated to neutrophils in the BAL and inversely correlated to the gestational age of prematurity. Elevation of IL-8 level in BAL on the first day of life was correlated to the development of CLD. Further studies showed that neonatal cord blood released significantly higher IL-8 but lower TNF-alpha levels after stimulation by endotoxin. The augmented IL-8 mRNA expression in cord blood was inhibited by actinomycin D but enhanced by cycloheximide, suggesting that IL-8 production is controlled by de novo transcriptional induction as well as posttranscriptional up-regulation of IL-8 by neonatal leukocytes, relating to the development of CLD. Thus, an appropriate modulation of initial IL-8 production in premature infants might be beneficial for the prevention of the development of CLD.

Adult↗

PubMed2005

Higher spontaneous and TNFalpha-induced apoptosis of neonatal blood granulocytes.

Granulocytes play an important role in inflammatory diseases. Neonates tend to develop granulocytopenia under sepsis and stress. It remains unclear whether apoptosis of neonatal granulocytes is different from that of adult granulocytes. In this study, we analyzed the discrepancy of granulocyte apoptosis between cord blood (CB) and adult blood (AB). We found that spontaneous and tumor necrosis factor-alpha (TNFalpha)-induced granulocyte apoptosis as determined by phosphatidylserine expression and DNA fragmentation were more prominent in CB granulocytes than AB granulocytes. CD95 ligand and TNFalpha levels were significantly higher in CB than in AB (p = 0.001 and p < 0.001, respectively). TNF receptor-2 and CD95 expression on CB granulocytes were not different from those on AB granulocytes. However, the TNF receptor-1 (TNFR1) expression was lower on CB granulocytes than that on AB granulocytes (69.98 +/- 7.32 versus 89.04 +/- 3.73%, p = 0.029). This decrease of TNFR1 expression on neonatal granulocytes might be related to a higher plasma TNFalpha level associated with an intrinsic defect on the dynamic change of membrane TNFR1 expression in neonatal granulocytes. The expression of anti-apoptotic molecule Bcl-2 in neonatal granulocytes was also lower than that in adult granulocytes (4.64 +/- 0.51 versus 7.24 +/- 1.17 unit/mg protein, p = 0.032). Moreover, another anti-apoptotic signal, nuclear factor-kappaB nuclear translocation, was also lower in CB than AB granulocytes. Results from this study suggest that higher plasma death ligands associated with lower anti-apoptotic molecules in granulocytes may act an important role in triggering neonatal granulocyte apoptosis.

Active Transport, Cell Nucleus↗

PubMed2005

Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass.

Prolonged glucocorticoid treatment is known to cause osteoporosis or aseptic necrosis. Secreted frizzled-related proteins 1 (SFRP1) and low-density lipoprotein-related protein 5 (LRP5), a Wnt protein antagonist and a coreceptor, have been found to regulate skeletogenesis. Whereas recent studies have reported that excess glucocorticoid promotes bone loss, the biological role of SFRP1 and LRP5 in regulating glucocorticoid attenuation of bone formation is not fully understood. We showed that a supraphysiological level of glucocorticoid enhanced SFRP1 but not LRP5 expression of primary mesenchymal cell cultures in vitro and osteoblasts at metaphyseal trabecular endosteum and chondrocytes at calcified cartilage in vivo. Glucocorticoid augmentation of SFRP1 expression was transcriptionally mediated. The inhibitory action of glucocorticoid on osteogenic differentiation appeared to be regulated by SFRP1 mediation of beta-catenin destabilization because knocking down SFRP1 by RNA interference abrogated the supraphysiological level of glucocorticoid attenuation of osteogenesis. Recombinant human SFRP1 reduced the promoting effect of physiological level of glucocorticoid on cytosolic beta-catenin accumulation, runt-related transcription factor-2 activation, and osteogenic activities. Glucocorticoid and recombinant human SFRP1 significantly increased osteochondral cell apoptosis associated with reduced mineral density, biomechanical properties, trabecular bone volume, and midshaft cortical bone areas in rat femurs. These findings suggest that SFRP1 modulates glucocorticoid-induced bone loss. Regulation of Wnt/SFRP signal transduction can be used in the future as an alternative strategy for the prevention of glucocorticoid-induced osteoporosis.

Animals↗

PubMed2005

Suppressed TGF-beta1 expression is correlated with up-regulation of matrix metalloproteinase-13 in keloid regression after flashlamp pulsed-dye laser treatment.

BACKGROUND AND OBJECTIVES: Flashlamp pulsed-dye lasers (PDLs) has shown effectiveness in the treatment of keloids. In this study, we investigated whether PDL treatments decreased transforming growth factor-beta1 (TGF-beta1)-induction and up-regulation of matrix metalloproteinase (MMP) expression in keloid regression. STUDY DESIGN/MATERIALS AND METHODS: Keloid tissues obtained from 10 patients with intra-lesional or punch biopsies before and 7 days after PDL treatments [fluence per pulse was 10-18 J/cm2 (mean 14.0 J/cm2)]. Immunohistochemical (IHC) staining of TGF-beta1 and MMP-1 and MMP-13 expressions in keloid tissue was performed. Western blot analysis of MMP-1 and MMP-13 expressions in extracellular matrix was evaluated. RESULTS: IHC staining indicated that expression of TGF-beta1 was significantly reduced in keloid tissues after PDL irradiation. MMP-13 but not MMP-1 expression on IHC staining significantly increased in extracellular matrix of keloid tissues after PDL treatment. Western blot analysis also showed MMP-13 but not MMP-1 significant increased in keloid tissues after PDL treatment. CONCLUSIONS: Regression of keloids regressed after PDL treatments are associated with down-regulation of TGF-beta1 expression and up-regulation of MMP-13 activity.

Adolescent↗

PubMed2005

Activation of ERK and p38 kinase mediated keloid fibroblast apoptosis after flashlamp pulsed-dye laser treatment.

BACKGROUND AND OBJECTIVES: Flashlamp pulsed-dye lasers (PDLs) revealed effective regression or arrest in patients with keloids in our clinical studies [Kuo YR et al., Laser Surg Med 2004;34:104-108]. In this study, we further investigated whether the induction of keloid regression seen with PDL treatment through activation in mitogen-activated protein (MAP) kinase and caspase promotes cell apoptosis and reduces fibroblast proliferation. STUDY DESIGN/MATERIALS AND METHODS: Keloid tissues were obtained from 10 patients with intralesional or punch biopsies prior to and 7 days after PDL treatments [fluence per pulse was 10-18 J/cm2 (mean 14 J/cm2)]. Prior to and after PDL treatments, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining and fragmented caspase-3 expression. MAP kinase activation as represented by extracellular signal-regulated kinase (ERK), p38 kinase (p38), and c-Jun N-terminal kinase (JNK) expression of keloid tissues was investigated by immunohistochemical (IHC) staining, respectively. RESULTS: IHC staining indicated that PCNA expression of fibroblasts was significantly reduced in keloid tissue after PDL irradiation. TUNEL assay revealed lower apoptotic cells expression in the keloid tissue prior to laser treatment. Following laser treatment, apoptotic cells with relatively strong DNA damage and fragmentation were seen in all keloid biopsy samples, especially in the keloid fibroblast population. The activation of ERK and p38 MAP kinase increased significantly in keloid tissue after PDL treatment. JNK was shown to be unchanged. CONCLUSIONS: The PDL treatment is shown to induce keloid regression through suppression of keloid fibroblast proliferation, induction of apoptosis, and upregulation of ERK and p38 MAP kinase activity.

Adolescent↗

PubMed2005

The effect of shock wave treatment at the tendon-bone interface-an histomorphological and biomechanical study in rabbits.

PURPOSE: This study was performed to investigate the effect of shock wave treatment on the healing at tendon-bone interface in rabbits. MATERIALS AND METHODS: Thirty-six New Zealand White rabbits were used in this study. The anterior cruciate ligament was excised and replaced with the long digital extensor. The right knees (study group) were treated with 500 impulses of shock waves at 14 kV, while the left knees (control group) received no shock waves. Histomorphological studies were performed in 24 rabbits at 1, 2, 4, 8, 12 and 24 weeks. Biomechanical studies were performed in 12 rabbits at 12 and 24 weeks. RESULTS: There was significantly more trabecular bone around the tendons noted in the study group compared with the control group at different time intervals after 4 weeks (P<0.05). The contacting between bone and tendon was significantly better in the study group than the control group after 8 weeks (P<0.05). The tensile strength of the tendon-bone interface was significantly higher in the study group than the control group at 24 weeks (P=0.018), whereas similar modes of graft failure were noted between the two groups. CONCLUSION: Shock wave treatment significantly improves the healing rate of the tendon-bone interface in a bone tunnel in rabbits. The effect of shock waves appears to be time-dependent.

Animals↗

PubMed2005

Acute diarrhea during pelvic irradiation: is small-bowel volume effect different in gynecologic patients with prior abdomen operation or not?

OBJECTIVE: To evaluate volume effect of small bowel for diarrhea during pelvic irradiation in gynecologic patients with or without prior abdomen operation. METHODS: From January 1996 through December 2003, 759 patients undergoing 4-field pelvic irradiation for cervical or uterine cancer were analyzed. Whole pelvic (WP), modified whole pelvic (MWP), or lower pelvic (LP) irradiation were delivered initially. According to contrast medium within small bowel in simulation films, we categorized the small-bowel volume of full dose related to WP fields as small-volume and large-volume groups. We recorded the severity of diarrhea until 39.6 Gy/22 fractions of pelvic irradiation. The actuarial rates of overall and moderate to severe diarrhea were compared among different groups. RESULTS: Significantly more large-volume distribution (85%) was noted in patients >60 years without prior operation (P < 0.001). Large-volume distribution was 53%, 65%, and 82% in post-operative patients with no diarrhea, mild diarrhea, and moderate to severe diarrhea (P = 0.002), respectively. The corresponding rate was 79%, 77%, and 80% in patients without prior abdomen operation (P = 0.869). In multivariate analysis, prior operation with LP fields (P = 0.005) and prior operation with small volume (P = 0.031) were significantly protective factors for overall diarrhea. The latter was also a protective factor for moderate to severe diarrhea (P = 0.026). Prior operation could diminish overall diarrhea in patients without simultaneous large-field (WP or MWP) and large-volume. Large volume was a significant factor of overall (P = 0.014) and moderate to severe (P = 0.004) diarrhea in large-field patients with operation. The volume effect did not exist in those patients without operation. CONCLUSION: Age and operation can change small-bowel distribution. Prior operation may attenuate diarrhea if irradiated volume of small bowel is small. There is a volume effect in post-operative rather than non-operative patients receiving large-field irradiation. More practical dose-volume evaluation of small bowel may be applied for volume effect in gynecologic patients without prior operation.

Abdomen↗

PubMed2005

Treatment for osteonecrosis of the femoral head: comparison of extracorporeal shock waves with core decompression and bone-grafting.

BACKGROUND: There is continuing controversy regarding the optimal treatment for patients with symptomatic early-stage osteonecrosis of the femoral head. We compared the results of noninvasive treatment with extracorporeal shock waves with those of core decompression and bone-grafting in similar groups of patients. METHODS: Patients with stage-I, II, or III osteonecrosis were randomly assigned to be treated either with shock waves or with core decompression and nonvascularized fibular grafting. The shock-wave group consisted of twenty-three patients (twenty-nine hips), and the surgical group consisted of twenty-five patients (twenty-eight hips). The patients in the two groups had similar demographic characteristics, duration and stage of disease, and duration of follow-up. The patients in the shock-wave group received a single treatment with 6000 impulses of shock waves at 28 kV to the affected hip. The evaluation parameters included clinical assessment of pain with a visual analog pain scale, Harris hip scores, and an assessment of activities of daily living and work capacity. Radiographic assessment was performed with serial plain radiographs and magnetic resonance imaging. RESULTS: Before treatment, the two groups had similar pain and Harris hip scores. At an average of twenty-five months after treatment, the pain and Harris hip scores in the shock-wave group were significantly improved compared with the pretreatment scores (p < 0.001). In this group, 79% of the hips were improved, 10% were unchanged, and 10% were worse. Of the hips treated with a nonvascularized fibular graft, 29% were improved, 36% were unchanged, and 36% were worse. In the shock-wave group, imaging studies showed regression of five of the thirteen lesions that had been designated as stage I or II before treatment and no regression of a stage-III lesion. Two stage-II and two stage-III lesions progressed. In the surgical group, four lesions regressed and fifteen (of the nineteen graded as stage I or II) progressed. The remaining nine lesions were unchanged. CONCLUSIONS: Extracorporeal shock-wave treatment appeared to be more effective than core decompression and nonvascularized fibular grafting in patients with early-stage osteonecrosis of the femoral head. Long-term results are needed to determine whether the effect of this novel method of treatment for osteonecrosis of the femoral head endures.

Adult↗

PubMed2004

Evolutionary optimization with data collocation for reverse engineering of biological networks.

MOTIVATION: Modern experimental biology is moving away from analyses of single elements to whole-organism measurements. Such measured time-course data contain a wealth of information about the structure and dynamic of the pathway or network. The dynamic modeling of the whole systems is formulated as a reverse problem that requires a well-suited mathematical model and a very efficient computational method to identify the model structure and parameters. Numerical integration for differential equations and finding global parameter values are still two major challenges in this field of the parameter estimation of nonlinear dynamic biological systems. RESULTS: We compare three techniques of parameter estimation for nonlinear dynamic biological systems. In the proposed scheme, the modified collocation method is applied to convert the differential equations to the system of algebraic equations. The observed time-course data are then substituted into the algebraic system equations to decouple system interactions in order to obtain the approximate model profiles. Hybrid differential evolution (HDE) with population size of five is able to find a global solution. The method is not only suited for parameter estimation but also can be applied for structure identification. The solution obtained by HDE is then used as the starting point for a local search method to yield the refined estimates.

Algorithms↗

PubMed2004

Nitrosoglutathione modulation of platelet activation and nitric oxide synthase expression in promotion of flap survival after ischemia/reperfusion injury.

BACKGROUND: Recent studies have shown that platelets play an important role in the pathogenesis of reperfusion injury. Using an inferior epigastric artery skin flap as a flap ischemia/reperfusion (I/R) injury model, we investigated whether the administration of a nitric oxide (NO) donor, nitrosoglutathione (GSNO), could decrease platelet activation and modulate the NO synthase (NOS) activity of platelets and promote flap survival. METHODS: Thirty minutes before flap reperfusion, normal saline (1 mL), nitrosoglutathione (GSNO 0.2, 0.6, 3 mg/kg), or N(G)-nitro-L-arginine-methyl ester (450 mg/kg) was injected intravenously in 10 rats, respectively. The p-selectin (CD62P) expression of platelet activation was detected by a flow cytometry. Immunohistochemical staining was performed to investigate the CD62P deposition on the microvasculature of the flap vessels. NOS isoform expression in the platelets was evaluated by Western blot. Tissue perfusion was monitored by using laser-Doppler flowmetry. Survival areas were assessed at 7 days postoperatively RESULTS: An optimal dose of GSNO (0.6 mg/kg), significantly decreased in CD62P expression on platelets (P < 0.001) and its deposition on the flap vessels, selectively suppressed iNOS induction of platelet, and significantly improved blood perfusion and the flap survival rate (59.8 +/- 4.9% versus 22.1 +/- 6.1%, P < 0.001). In contrast, the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester, although inhibiting iNOS expression of platelets, compromised platelet activation, tissue perfusion, and flap survival. CONCLUSION: This study suggests that GSNO can appropriately donate NO to suppress platelet activation and platelet iNOS induction, resulting in less platelet activation, better blood perfusion, and flap survival after I/R injury.

Animals↗

PubMed2004

Nitric oxide donor increases osteoprotegerin production and osteoclastogenesis inhibitory activity in bone marrow stromal cells from ovariectomized rats.

Nitric oxide (NO) has emerged as a potent regulator useful in alleviating estrogen deficiency bone loss. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) play important roles in regulating osteoclastogenesis. Although recent studies have reported NO donor attenuation of bone loss, the effect of NO donor on OPG and RANKL expression of osteogenic stromal cells and bone microenvironment in ovariectomized rats is not fully understood. Here, we showed that optimal NO donor treatment [2,2'-(hydroxynitrosohydrazino)bis-ethanamine; 15 microm] increased OPG, but not RANKL, levels in bone marrow stromal cells from ovariectomized rats. NO donor augmentation of OPG synthesis was transcriptionally mediated. The stimulatory action of NO donor on OPG expression appeared to be regulated by tyrosine kinase-dependent activation of Cbfa1/Runx2 binding to the OPG promoter, because cell cultures pretreated with tyrosine kinase inhibitor (herbimycin A), but not with protein kinase A inhibitor (calphostain C) or protein kinase C inhibitor [(Rp)-cAMP] significantly reduced NO-augmented Runx2 activation and OPG levels. Conditioned medium from NO donor-treated cells inhibited macrophage-colony-stimulating factor and RANKL-induced osteoclast formation of macrophage-colony-stimulating factor-dependent bone marrow macrophages. Neutralization with anti-OPG antibodies abolished the inhibitory effect of conditioned medium on osteoclastogenesis. Immunohistochemical observation also showed that 2,2'-(hydroxynitrosohydrazino)bis-ethanamine increased OPG expression of osteochondral cells located at metaphyseal endosteum and calcified cartilage of proximal femurs in ovariectomized rats. These findings suggest that NO donor can be an alternative pharmacological strategy for regulating bone resorption.

Animals↗

PubMed2004

Shockwave stimulates oxygen radical-mediated osteogenesis of the mesenchymal cells from human umbilical cord blood.

UNLABELLED: Human umbilical cord blood (HUCB) mesenchymal progenitor cells expressed stro-1 or CD44 or CD29, and subsequently, differentiated toward osteogenic lineage. Physical shockwave treatment increased osteogenic activity of HUCB mesenchymal progenitor cells through superoxide-mediated TGF-beta1 induction. Transplantation of shockwave-treated HUCB mesenchymal progenitor cells enhanced healing of segmental femoral defect in severe combined immunodeficiency disease (SCID) mice. INTRODUCTION: Mesenchymal progenitor cells (MPCs) in the bone marrow are precursors to bone development. It remains uncertain whether MPCs are present in human umbilical cord blood (HUCB) and are capable of differentiating into osteogenic cell lineage. Extending from a model of shockwave (SW) promotion of bone marrow stromal cell differentiation toward osteoprogenitors in rats, we further investigated how physical SW mediated biological responses in regulating osteogenic differentiation of HUCB MPCs. MATERIALS AND METHODS: HUCB was subjected to SW treatment at different energy flux densities and impulses. Colony-forming units-stroma (CFU-Stroma), osteogenic activities (Cbfa1/Runx2 expression, bone alkaline phosphatase activity, and bone nodule formation), and bone formation by heterologous transplantation into SCID mice were assessed. RESULTS: Few CD34+ stem cells (1.3%) and stro-1+ cells (1.0%) were present in the freshly prepared mononuclear cells (MNCs) from HUCB. The number of stro-1+ cells, but not CD34+, increased to 72.4% in the adherent cell culture over 6 days. Stro-1+ cells co-expressed CD44 and CD29 markers and grew into CFU-Stroma that matured into bone nodules. We found that the SW treatment (0.16 mJ/mm2 energy flux density, 200 impulses) elicited superoxide production and promoted formation of CFU-Stroma, but not of hematopoietic CFU-Mix. SW also enhanced the production of transforming growth factor (TGF)-beta1, but not of interleukin (IL)-3 or granulocyte monocyte-colony stimulating factor (GM-CSF). Neutralization of TGF-beta1 significantly reduced SW-promoted CFU-Stroma formation. Superoxide scavenging by superoxide dismutase blocked SW enhancement of TGF-beta1 production and formation of CFU-Stroma. Administration of SW-treated HUCB MPCs to SCID mice with femoral segmental defects facilitated dense, bridging callus and gap closure. CONCLUSION: HUCB MPCs subjected to SW treatment is a potential source for stem cells useful in the treatment of orthopedic disorders. An optimal physical SW treatment enhanced osteogenesis through superoxide-mediated TGF-beta1 production. Physical stimulation is an alternative method for extending mesenchymal stem cells of HUCB.

Animals↗

PubMed2004

Flashlamp pulsed dye laser (PDL) suppression of keloid proliferation through down-regulation of TGF-beta1 expression and extracellular matrix expression.

BACKGROUND AND OBJECTIVES: Keloids have been treated with flashlamp pulsed dye lasers (PDLs) with good results. We investigated whether PDL treatments induced keloid regression by decreasing growth factor-beta(1) (TGF-beta(1)) induction, thereby reducing fibroblast proliferation and collagen deposition. STUDY DESIGN/MATERIALS AND METHODS: Clinical evaluation and photography documented keloid height/texture, erythema, and pliability before and after PDL treatments scheduled at 2-month intervals in 30 patients. Fluence per pulse was 10-18 J/cm(2) (mean 14.0 J/cm(2)). Immunohistochemical (IHC) staining of TGF-beta(1), proliferating cell nuclear antigen (PCNA), and collagen (types I and III) in extra-cellular matrix was performed on 10 intra-lesional or punch biopsies obtained before and 7 days after PDL treatments. RESULTS: Twelve months after final PDL treatments, keloid regression ( >/= 50%) had occurred in 26/30 patients in whom erythema and surface irregularities had been reduced and pliability had been increased. In 4/30 patients, no changes in keloids had occurred after 12 months. Multiple treatments ( > 6) yielded better results than fewer treatments: 79% versus 50%, respectively. Marked keloid regression ( >/= 90%) occurred in two patients who had received more than 10 treatments. IHC staining indicated that expression of TGF-beta(1), PCNA and collagen type III, but not type I, was significantly reduced in keloid fibroblasts after PDL irradiation. CONCLUSIONS: Keloids regressed following PDL-induced reduction in TGF-beta(1) expression, fibroblast proliferation, and collagen type III deposition. More than six PDL treatments at 2-month intervals provided the best results.

Adolescent↗