scholarly journals Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation

2010 ◽  
Vol 25 (11) ◽  
pp. 2447-2459 ◽  
Author(s):  
Liang Chen ◽  
Wei Jiang ◽  
Jiayi Huang ◽  
Bai-Cheng He ◽  
Guo-Wei Zuo ◽  
...  
Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S432-S433
Author(s):  
Liang Chen ◽  
Wei Jiang ◽  
Baicheng He ◽  
Tongchuan He ◽  
Zhongliang Deng

1998 ◽  
Vol 83 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Gordon L. Klein ◽  
Steven E. Wolf ◽  
Craig B. Langman ◽  
Clifford J. Rosen ◽  
Subburaman Mohan ◽  
...  

Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone formation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg·day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 ± 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level. IGFBP-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.


1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid

Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 ± 14 yr of age) were treated with IGF-I (5 μg/kg/h in a continuous sc infusion) and GH (0.03 IU/kg/daily sc injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2–3 days of both treatments (P < 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. Conclusions: Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1α-hydroxylase activity in vivo.


2012 ◽  
Vol 8 (3) ◽  
pp. 346-356 ◽  
Author(s):  
Sainan Wang ◽  
Jinquan Mu ◽  
Zhipeng Fan ◽  
Yan Yu ◽  
Ming Yan ◽  
...  

2016 ◽  
Vol 397 (8) ◽  
pp. 765-775 ◽  
Author(s):  
Chang-jun Pi ◽  
Kai-lu Liang ◽  
Zhen-yong Ke ◽  
Fu Chen ◽  
Yun Cheng ◽  
...  

Abstract Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.


2019 ◽  
Vol 20 (5) ◽  
pp. 1253 ◽  
Author(s):  
Donghun Lee ◽  
Sung Lee ◽  
Namhoon Cho ◽  
Young-Sik Kim ◽  
Jungbin Song ◽  
...  

Eleutherococcus extract mixture (EEM) is an herbal mixture of dried stem of Eleutherococcus sessiliflorus and germinated barley, which has been highly effective, in previous screening and among the traditional medicines to tonify innate qi and acquired qi, respectively. In this study, we investigate the effects of EEM on endochondral bone formation. Female adolescent rats were given EEM, growth hormone or vehicle for 10 days. Tetracycline was intraperitoneally injected to light the fluorescent band 72 h before sacrifice to determine endochondral bone formation. In order to evaluate endocrine or paracrine/autocrine mechanisms, expressions of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), or bone morphogenetic protein 2 (BMP2) were evaluated after EEM administration in liver or growth plate (GP). EEM oral administration significantly increased endochondral bone formation and proliferative and hypertrophic zonal heights of tibial GP. EEM also upregulated hepatic IGF1 and IGFBP3 mRNA expressions, and IGF1 and BMP2 expressions in GP. Taken together, EEM increases endochondral bone formation through stimulating proliferation and hypertrophy with upregulation of hepatic IGF1 and IGFBP3 expressions. Considering immunohistochemical studies, the effect of EEM may be due to increased local IGF1 and BMP2 expression in GP, which may be considered growth hormone (GH)-dependent endocrine and autocrine/paracrine pathways.


Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 472
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Jayasingha Arachchige Chathuranga Chanaka Jayasingha ◽  
Yung Hyun Choi ◽  
Eui Kyun Park ◽  
You-Jin Jeon ◽  
...  

Fermented oyster (Crassostrea gigas) extract (FO) prevents ovariectomy-induced osteoporosis by inhibiting osteoclastogenesis and activating osteogenesis. However, the molecular mechanisms underlying FO-mediated bone formation and growth rate are unclear. In the current study, we found that FO significantly upregulated the expression of growth-promoting genes in zebrafish larvae including insulin-like growth factor 1 (zigf-1), insulin-like growth factor binding protein 3 (zigfbp-3), growth hormone-1 (zgh-1), growth hormone receptor-1 (zghr-1), growth hormone receptor alpha (zghra), glucokinase (zgck), and cholecystokinin (zccka). In addition, zebrafish larvae treated with 100 μg/mL FO increased in total body length (3.89 ± 0.13 mm) at 12 days post fertilization (dpf) compared to untreated larvae (3.69 ± 0.02 mm); this effect was comparable to that of the β-glycerophosphate-treated zebrafish larvae (4.00 ± 0.02 mm). Furthermore, FO time- and dose-dependently increased the extracellular release of IGF-1 from preosteoblast MC3T3-E1 cells, which was accompanied by high expression of IGF-1. Pharmacological inhibition of IGF-1 receptor (IGF-1R) using picropodophyllin (PPP) significantly reduced FO-mediated vertebrae formation (from 9.19 ± 0.31 to 5.53 ± 0.35) and growth performance (from 3.91 ± 0.02 to 3.69 ± 0.01 mm) in zebrafish larvae at 9 dpf. Similarly, PPP significantly decreased FO-induced calcium deposition in MC3T3-E1 cells by inhibiting GSK-3β phosphorylation at Ser9. Additionally, DOI hydrochloride, a potent stabilizer of GSK-3β, reduced FO-induced nuclear translocation of RUNX2. Transient knockdown of IGF-1Rα/β using specific silencing RNA also resulted in a significant decrease in calcium deposition and reduction in GSK-3β phosphorylation at Ser9 in MC3T3-E1 cells. Altogether, these results indicate that FO increased phosphorylated GSK-3β at Ser9 by activating the autocrine IGF-1-mediated IGF-1R signaling pathway, thereby promoting osteogenesis and growth performance. Therefore, FO is a potential nutritional supplement for bone formation and growth.


2013 ◽  
Vol 92 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Takuo Kubota ◽  
Hashem Z. Elalieh ◽  
Neema Saless ◽  
Chak Fong ◽  
Yongmei Wang ◽  
...  

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