Therapy with recombinant human IGF-1 for children with primary insulin-like growth factor-I deficiency

Backeljauw, Philippe

doi:10.1016/j.ghir.2020.01.001

Cited by 7 publications

(5 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At present, IGF-1 is considered to be widely involved in bone growth and development. It has been reported that severe IGF-1 deficiency can cause short stature, and IGF-1 can significantly improve this condition ( 7 ). A previous study has confirmed that IGF-1 is positively correlated with bone density and that IGF-1 in the blood of patients with osteoporosis is significantly reduced ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Insulin growth factor‑1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β‑catenin pathway

Feng

Meng

2021

Exp Ther Med

View full text Add to dashboard Cite

Bone marrow mesenchymal stem cells (BMSCs) are stem cells that exist in bone marrow tissue and have osteogenic differentiation potential. Insulin growth factor-1 (IGF-1) plays a key role in the proliferation and osteogenic differentiation of BMSCs. However, the specific mechanism of IGF-1 in cell proliferation and osteogenic differentiation remains unclear. In the present study, BMSCs were transfected with lentivirus carrying the siRNA-Wnt3a gene, and the Wnt3a level in BMSCs was revealed to be reduced by western blotting, real-time quantitative polymerase chain reaction and immunofluorescence detection. Then, BMSCs were treated with 80 ng/ml IGF-1 in complete medium for 5 days. CCK-8 and cell cycle assays revealed that cell proliferation was significantly decreased in the siRNA-Wnt3a group than in the control group. The protein and mRNA levels of β-catenin and cyclin D1 were significantly downregulated in the siRNA-Wnt3a group compared with the control group. In addition, BMSCs were treated with IGF-1 in osteogenic differentiation medium for 7 and 21 days, and alkaline phosphatase staining and Alizarin Red staining demonstrated significantly reduced osteogenic differentiation ability in the siRNA-Wnt3a group compared with the control group. Furthermore, the protein and mRNA levels of β-catenin, RUNX2, and OPN were downregulated compared with the control group. Our findings revealed that IGF-1 promoted the proliferation and differentiation of BMSCs at least partially through the Wnt/β-catenin pathway. These findings provided new insight into the clinical treatment of bone disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Insulin growth factor‑1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β‑catenin pathway

Feng

Meng

2021

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…These numbers clearly show that this patient group is undertreated, possibly because of concern over the risk of recurrence or the occurrence of new malignancies. Risks of GHT in central nervous system tumors among pediatric and adult patients are still not fully clear [ 35 ]. Several recent studies have shown no association between GHT and new malignancies, either recurrence or secondary tumor, among childhood tumor survivors [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Pre- and postdiagnosis growth failure, adult short stature, and untreated growth hormone deficiency in radiotherapy-treated long-term survivors of childhood brain tumor

Anttonen

Remes²,

Arikoski³

et al. 2022

PLoS ONE

View full text Add to dashboard Cite

Purpose Growth failure is common in radiotherapy-treated long-term survivors of pediatric brain tumors, but studies on longitudinal growth in this patient group are lacking. Here, the aim was to assess the changes in growth patterns before and after brain tumor diagnosis, the adult height, and the risk factors for compromised growth. The incidence and treatment practices of growth hormone deficiency were analyzed. Methods A cohort of 73 survivors of childhood brain tumor (median age 27.2 years, range 16.2 to 43.8 years) was studied after a median follow-up period of 20.4 years from diagnosis (IQR 14.9 to 22.9 years). Patients were treated in five university hospitals in Finland between 1970 and 2008. Growth curves, final height, and patient- and disease-related risk factors for compromised growth during different growth periods were analyzed. Laboratory analyses for IGF-1 and IGFBP-3 were performed at the follow-up. Results Growth failure was evident at diagnosis, with a mean height decline of -0.6 SDS (standard deviation score) from birth (95% CI -1.15 to -0.05). Mean height SDS decline after the diagnosis was -1.09 SDS (95%CI -1.51 to -0.66). At follow-up, 37% of the study subjects (27/73) had true short stature (height < -2 SDS). The mean height deficit corrected for target height was -1.9 SDS (95% CI -1.45 to -2.40). Growth failure was associated with the age at diagnosis, corticosteroid dose, radiotherapy modality and mean dose of irradiation in the thalamic area. Low IGF-1 level (below -2.0 SDS) was found in 32% (23/72), and untreated growth hormone deficiency in 40% (29/72) of the subjects. Conclusion Longitudinal growth impairment was common in radiotherapy-treated survivors of childhood brain tumor, resulting in compromised adult height. Loss of growth potential was evident already at diagnosis and further accelerated by the treatments. At young adulthood, unrecognized growth hormone deficiency was common.

show abstract

“…IGF1 significantly promotes OBD [ 38 , 39 ] and increased the bone density of rodents both in HU modeling and in a space shuttle [ 40 , 41 ]. Clinical trials have been conducted on the effect of the administration of recombinant IGF1 on bone healing [ 42 , 43 ]. Notably, IGF1 has also been found to promote adipogenic differentiation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of Focal Adhesion Kinase Restores Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation via Wnt/Β-Catenin Pathway

Fan

Cooper

et al. 2022

IJMS

View full text Add to dashboard Cite

Simulated microgravity (SMG) inhibits osteoblast differentiation (OBD) and induces bone loss via the inhibition of the Wnt/β-catenin pathway. However, the mechanism by which SMG alters the Wnt/β-catenin pathway is unknown. We previously demonstrated that SMG altered the focal adhesion kinase (FAK)-regulated mTORC1, AMPK and ERK1/2 pathways, leading to the inhibition of tumor cell proliferation/metastasis and promoting cell apoptosis. To examine whether FAK similarly mediates SMG-dependent changes to Wnt/β-catenin in osteoblasts, we characterized mouse MC3T3-E1 cells cultured under clinostat-modeled SMG (µg) conditions. Compared to cells cultured under ground (1 g) conditions, SMG reduces focal adhesions, alters cytoskeleton structures, and down-regulates FAK, Wnt/β-catenin and Wnt/β-catenin-regulated molecules. Consequently, protein-2 (BMP2), type-1 collagen (COL1), alkaline-phosphatase activity and matrix mineralization are all inhibited. In the mouse hindlimb unloading (HU) model, SMG-affected tibial trabecular bone loss is significantly reduced, according to histological and micro-computed tomography analyses. Interestingly, the FAK activator, cytotoxic necrotizing factor-1 (CNF1), significantly suppresses all of the SMG-induced alterations in MC3T3-E1 cells and the HU model. Therefore, our data demonstrate the critical role of FAK in the SMG-induced inhibition of OBD and bone loss via the Wnt/β-catenin pathway, offering FAK signaling as a new therapeutic target not only for astronauts at risk of OBD inhibition and bone loss, but also osteoporotic patients.

show abstract

Therapy with recombinant human IGF-1 for children with primary insulin-like growth factor-I deficiency

Cited by 7 publications

References 22 publications

Insulin growth factor‑1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β‑catenin pathway

Insulin growth factor‑1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β‑catenin pathway

Pre- and postdiagnosis growth failure, adult short stature, and untreated growth hormone deficiency in radiotherapy-treated long-term survivors of childhood brain tumor

Activation of Focal Adhesion Kinase Restores Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation via Wnt/Β-Catenin Pathway

Contact Info

Product

Resources

About