scholarly journals Human Recombinant Fibroblast Growth Factor-18 (Sprifermin), Enhances Cartilage Healing in a Cartilage Injury Model

2020 ◽  
Author(s):  
Honey Hendesi ◽  
Suzanne Stewart ◽  
Michelle L Gibison ◽  
Hans Guehring ◽  
Dean W. Richardson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Outcome Measures ◽  
Matrix Protein ◽  
Secondary Outcome ◽  
Fibroblast Growth ◽  
Treatment Benefit ◽  
Cartilage Healing ◽  
Active Population ◽  
The Impact

Abstract Background: Post traumatic osteoarthritis is a disabling condition impacting mostly young and active population. In the present study we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. Methods: For the purpose if this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 mg) or with saline, hyaluronan (HA), and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures we performed histological evaluations and performed gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix protein (COMP) in three regions of interest. As secondary outcome measures we examined animal’s lameness, performed arthroscopic, radiographic, and CT scan imaging, and gross morphology assessment. Results: We detected the highest treatment benefit following 100 mg sprifermin treatment. Overall histological assessment showed an improvement in the kissing region and expression of constitutive genes showed a concentration dependent enhancement, especially in the peri-lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose-treatment groups were combined. Conclusion: Our results demonstrated for the first time, an enhancement in outcomes of the microfracture treatment following sprifermin treatment, suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.

Fibroblast growth factor 21 (FGF-21) in obese children: no relationship to growth, IGF-1, and IGFBP-3

2016 ◽  
Vol 30 (2) ◽  
Author(s):  
Thomas Reinehr ◽  
Christian L. Roth ◽  
Joachim Woelfle
Keyword(s):  
Weight Loss ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Critical Role ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Obese Children ◽  
Pubertal Stage ◽  
The Impact ◽  
Igfbp 3

AbstractBackground:Fibroblast growth factor 21 (FGF-21) is a hepatic protein that plays a critical role in liver, adipose tissue, and bone metabolism. Animal models reported an increase of FGF-21 and associated growth disturbances in undernutrition. Therefore, we studied the impact of weight loss in obese children on growth, FGF-21, and insulin-like factor 1 (IGF-1) concentrations.Methods:We analyzed height, serum concentrations of FGF-21, IGF-1, IGFBP-3, leptin, and insulin at baseline and 1 year later in 30 obese children with substantial weight loss (reduction >0.5 BMI-SDS) and in 30 obese children of similar age, gender, and pubertal stage with stable BMI-SDS. All children participated in a 1-year lifestyle intervention. Height and IGF-1 was transformed to standard deviation score (SDS). Multiple linear regression analyses adjusted for age, gender, and pubertal stage were performed.Results:At baseline, height-SDS was significantly related to IGF-1-SDS (β-coefficient 0.68 95% confidence interval (95% CI)±0.49; p=0.008) and leptin (β-coefficient 0.042 95% CI±0.030; p=0.008), but not to FGF-21 or insulin. FGF-21 was not significantly associated with IGF-1 or IGFBP-3. In longitudinal analysis, changes of FGF-21 were not significantly related to changes of height, IGF-1-SDS or IGFBP-3. However, in the subgroup of 30 children with substantial BMI-SDS reduction, FGF-21, leptin, insulin, and HOMA decreased significantly.Conclusion:As there was no significant association between FGF-21 and growth or IGF-1 both in cross-sectional and longitudinal analyses, these findings do not support the hypothesis that FGF-21 is involved in growth of obese children. Further studies are necessary to understand the multiple alterations in the growth hormone (GH) axis in obese children.

The impact of LDLR function on fibroblast growth factor 21 levels

2015 ◽  
Vol 241 (2) ◽  
pp. 322-325
Author(s):  
Joost Besseling ◽  
Kwok Leung Ong ◽  
Roeland Huijgen ◽  
Kerry-Anne Rye ◽  
G.Kees Hovingh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
The Impact

Differential Impacts of Intravenous Iron Administration and Iron-Containing Phosphate Binders on Serum Intact Fibroblast Growth Factor 23 Levels

2019 ◽  
Vol 47 (Suppl. 2) ◽  
pp. 63-69 ◽  
Author(s):  
Hirokazu Honda ◽  
Kenji Tanaka ◽  
Tetsuo Michihata ◽  
Keigo Shibagaki ◽  
Toshitaka Yuza ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Iron Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Intravenous Iron ◽  
Phosphate Binders ◽  
Fibroblast Growth ◽  
Iron Administration ◽  
Iron Treatment ◽  
The Impact

Aims: This study assessed the impact of iron administration on serum fibroblast growth factor 23 (FGF23) levels. Methods: Of 123 hemodialysis (HD) patients treated with erythropoiesis-stimulating agents, 22 received once-weekly intravenous iron and 17 received daily oral iron with iron-containing phosphate binders. Intact FGF23 and biomarkers of iron metabolism were measured from blood samples drawn before each HD session, at baseline and on days 3, 5, 7, and 14. Results: Phosphate levels did not differ among the 3 groups during the 14-day period. Ferritin levels were significantly increased in both iron treatment groups compared with the non-iron treatment group, but changes in transferrin saturation levels were similar in the intravenous iron and non-iron groups. However, intact FGF23 levels were continuously higher in the intravenous iron group than those in the other groups. Conclusion: Intravenous iron administration may influence intact FGF23 levels in HD patients independently of phosphate and iron metabolism.

scholarly journals Levels of Circulating Fibroblast Growth Factor 23 (FGF23) and Prognosis in Cancer Patients with Bone Metastases

2019 ◽  
Vol 20 (3) ◽  
pp. 695 ◽  
Author(s):  
André Mansinho ◽  
Arlindo R. Ferreira ◽  
Sandra Casimiro ◽  
Irina Alho ◽  
Inês Vendrell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Metastases ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Patients With Cancer ◽  
Skeletal Related Events ◽  
Baseline Characteristics ◽  
The Impact

The fibroblast growth factor (FGF) signaling pathway plays a key role in tumorigenesis and is recognized as a potential therapeutic target. In this study, the authors aimed to assess the impact of serum FGF23 levels in the prognosis of patients with cancer and bone metastases from solid tumors. A cohort of 112 patients with cancer and metastatic bone disease were treated with bone-targeted agents (BTA). Serum baseline FGF23 was quantified by ELISA and dichotomized in FGF23high and FGF23low groups. Additionally, the association between FGF23 and overall survival (OS) and time to skeletal-related events (TTSRE) was investigated. Baseline characteristics were balanced between groups, except for the median urinary N-terminal telopeptide (uNTX) level. After a median follow-up of 26.0 months, a median OS of 34.4 and 12.2 months was found in the FGF23low and FGF23high groups, respectively (multivariate HR 0.18, 95% CI 0.07–0.44, p = 0.001; univariate HR 0.27, p = 0.001). Additionally, TTSRE was significantly longer for patients with FGF23low (13.0 vs 2.0 months, p = 0.04). Overall, this study found that patients with FGF23low at baseline had longer OS and TTSRE. Further studies are warranted to define its role as a prognostic biomarker and in the use of drugs targeting the FGF axis.

scholarly journals Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients

2020 ◽  
Vol 184 (2) ◽  
pp. 311-324
Author(s):  
Ramona Erber ◽  
Matthias Rübner ◽  
Simon Davenport ◽  
Sven Hauke ◽  
Matthias W. Beckmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Statistical Significance ◽  
Growth Factor Receptor ◽  
Small Sample ◽  
Fibroblast Growth ◽  
Luminal B ◽  
The Impact

Abstract Purpose Various aberrations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3 are found in different cancers, including breast cancer (BC). This study analyzed the impact of FGFR amplification on the BC prognosis. Methods The study included 894 BC patients. The amplification rates of FGFR1, FGFR2, and FGFR3 were evaluated on tissue microarrays using fluorescence in situ hybridization (FISH). Associations between these parameters and prognosis were analyzed using multivariate Cox regression analyses. Results FGFR1 FISH was assessable in 503 samples, FGFR2 FISH in 447, and FGFR3 FISH in 562. The FGFR1 amplification rate was 6.6% (n = 33). Increased FGFR2 copy numbers were seen in 0.9% (n = 4); only one patient had FGFR3 amplification (0.2%). Most patients with FGFR1 amplification had luminal B-like tumors (69.7%, n = 23); only 32.6% (n = 153) of patients without FGFR1 amplification had luminal B-like BC. Other patient and tumor characteristics appeared similar between these two groups. Observed outcome differences between BC patients with and without FGFR1 amplification did not achieve statistical significance; however, there was a trend toward poorer distant metastasis-free survival in BC patients with FGFR1 amplification (HR = 2.08; 95% CI 0.98 to 4.39, P = 0.05). Conclusion FGFR1 amplification occurs most frequently in patients with luminal B-like BC. The study showed a nonsignificant correlation with the prognosis, probably due to the small sample size. Further research is therefore needed to address the role of FGFR1 amplifications in early BC patients. FGFR2 and FGFR3 amplifications are rare in patients with primary BC.

Recombinant Fibroblast Growth Factor‐18 (Sprifermin), Enhances Microfracture Induced Cartilage Healing

2021 ◽  
Author(s):  
Honey Hendesi ◽  
Suzanne Stewart ◽  
Michelle L Gibison ◽  
Hans Guehring ◽  
Dean W. Richardson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Cartilage Healing

scholarly journals Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1764-1774 ◽  
Author(s):  
Quanxi Li ◽  
Juanmahel Davila ◽  
Athilakshmi Kannan ◽  
Jodi A. Flaws ◽  
Milan K. Bagchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bisphenol A ◽  
Fibroblast Growth Factor ◽  
Early Pregnancy ◽  
Chronic Exposure ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Fibroblast Growth ◽  
Uterine Function ◽  
The Impact

Abstract Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plastics and epoxy resins, has received much attention in female reproductive health due to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study, we addressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy.

scholarly journals Responses of gut and pancreatic hormones, bile acids, and fibroblast growth factor-21 differ to glucose, protein, and fat ingestion after gastric bypass surgery

2020 ◽  
Vol 318 (4) ◽  
pp. G661-G672 ◽  
Author(s):  
Christian Zinck Jensen ◽  
Kirstine N. Bojsen-Møller ◽  
Maria S. Svane ◽  
Line M. Holst ◽  
Kjeld Hermansen ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Growth Factor ◽  
Bile Acids ◽  
Fibroblast Growth Factor ◽  
Gut Hormones ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Control Subjects ◽  
Hormone Responses ◽  
The Impact

Postprandial gut hormone responses change after Roux-en-Y gastric bypass (RYGB), and we investigated the impact of glucose, protein, and fat (with and without pancreas lipase inhibition) on plasma responses of gut and pancreas hormones, bile acids, and fibroblast growth factor 21 (FGF-21) after RYGB and in nonoperated control subjects. In a randomized, crossover study 10 RYGB operated and 8 healthy weight-matched control subjects were administered 4 different 4-h isocaloric (200 kcal) liquid meal tests containing >90 energy (E)% of either glucose, protein (whey protein), or fat (butter with and without orlistat). The primary outcome was glucagon-like peptide-1 (GLP-1) secretion (area under the curve above baseline). Secondary outcomes included responses of peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), glicentin, neurotensin, ghrelin, insulin, glucagon, bile acids, and FGF-21. In the RYGB group the responses of GLP-1, GIP, glicentin, FGF-21, and C-peptide were increased after glucose compared with the other meals. The neurotensin and bile acids responses were greater after fat, while the glucagon and CCK responses were greater after protein ingestion. Furthermore, compared with control subjects, RYGB subjects had greater responses of total PYY after glucose, glucagon after glucose and fat, glicentin after glucose and protein, and GLP-1 and neurotensin after all meals, while GIP and CCK responses were lower after fat. Ghrelin responses did not differ between meals or between groups. Orlistat reduced all hormone responses to fat ingestion, except for ghrelin in the RYGB group. In conclusion, after RYGB glucose is a more potent stimulator of most gut hormones, especially for the marked increased secretion of GLP-1 compared with fat and protein. NEW & NOTEWORTHY We investigated the impact of glucose, protein, and fat meals on intestinal and pancreatic hormones, bile acid, and fibroblast growth factor 21 (FGF-21) secretion in gastric bypass-operated patients compared with matched nonoperated individuals. The fat meal was administered with and without a pancreas lipase inhibitor. We found that the impact of the different meals on gut hormones, bile, and FGF 21 secretion differ and was different from the responses observed in nonoperated control subjects.

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