Insulin enhances the growth of cartilage in organ and tissue cultures of mouse neonatal mandibular condyle

Maor, Gila; Silbermann, Michael; Mark, Klaus von der; Heingard, Dick; Laron, Zvi

doi:10.1007/bf00296654

Cited by 37 publications

(25 citation statements)

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“…The presence of Glut4 protein in the growing bone plate was also demonstrated in a rat model (38). The current study further supports the notion that MC organ culture can serve as a reliable model for studies concerning hormonal modulations of skeletal growth (14,26,28,29). Using this model, we have now shown that both insulin and IGF-I stimulate chondrocyte proliferation resulting in an overall increase in the growth of the MC.…”

Section: Discussionsupporting

confidence: 84%

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GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Maor

Vasiliver-Shamis

Hazan-Brill

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Skeletal growth, taking place in the cartilaginous growth plates of long bones, consumes high levels of glucose for both metabolic and anabolic purposes. We previously showed that Glut4 is present in growing bone and is decreased in diabetes. In the present study, we examined the hypothesis that in bone, GLUT4 gene expression and function are regulated via the IGF-I receptor (IGF-IR) and that Glut4 plays an important role in bone growth. Insulin and IGF-I actions on skeletal growth and glucose uptake were determined using mandibular condyle (MC) organ cultures and MC-derived primary cell cultures (MCDC). Chondrogenesis was determined by following proliferation and differentiation activities using immunohistochemical (IHC) analysis of proliferating cell nuclear antigen and type II collagen expression, respectively. Overall condylar growth was assessed morphometrically. GLUT4 mRNA and protein levels were determined using in situ hybridization and IHC, respectively. Glut4 translocation to the cell membrane was assessed using confocal microscopy analysis of GFP-Glut4 fusion-transfected cells and immunogold and electron microscopy on MC sections; glucose uptake was assayed by 2-deoxyglucose (2-DOG) uptake. Both IGF-I and insulin-stimulated glucose uptake in MCDC, with IGF-I being tenfold more potent than insulin. Blockage of IGF-IR abrogated both IGF-I- and insulin-induced chondrogenesis and glucose metabolism. IGF-I, but not insulin, induced Glut4 translocation to the plasma membrane. Additionally, insulin induced both GLUT4 and IGF-IR gene expression and improved condylar growth in insulin receptor knockout mice-derived MC. Moreover, silencing of GLUT4 gene in MCDC culture abolished both IGF-I-induced glucose uptake and chondrocytic proliferation and differentiation. In growing bone, the IGF-IR pathway stimulates Glut4 translocation and enhances glucose uptake. Moreover, intact Glut4 cellular levels and translocation machinery are essential for early skeletal growth.

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Section: Discussionsupporting

confidence: 84%

“…MC organ cultures were prepared as previously described (14,29). Briefly, MC were dissected from 5-to 6-day-old ICR mice and thoroughly washed in cold Hank's buffer.…”

Section: Organ Culturementioning

confidence: 99%

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Maor

Vasiliver-Shamis

Hazan-Brill

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…It has been suggested that leptin [28] and IGF-1 [8] might contribute to BA advancement in obesity, although recent work by Sopher et al [6] showed no association between these parameters and BA advancement. Future studies in larger cohorts should include these parameters to clarify the role these factors play in this matter.…”

Section: Discussionmentioning

confidence: 98%

Determinants of Advanced Bone Age in Childhood Obesity

et al. 2017

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Background: Childhood obesity is associated with advanced bone age (BA). Previous studies suggest that androgens, oestrogens, sex hormone-binding globulin, and insulin are responsible for this phenomenon, but results are contradictory and might be biased by confounders. We aim to elucidate this matter by applying a multivariate approach. Method: We performed a correlation analysis of BA standard deviation score (SDS) with age- and sex-specific SDS for androgens, oestrogens, and with indicators of insulin secretion derived from oral glucose tolerance testing, in a group of obese children. A multivariate analysis was performed to investigate which parameters were independently predictive of BA SDS. Results: In this cohort (n = 101; mean age 10.9 years; mean BA 11.8 years; mean BMI SDS 3.3), BMI SDS was significantly correlated to BA SDS (r = 0.55, p < 0.001). In a regression analysis in the total cohort (B = 0.27, p < 0.001) as well as in females (B = 0.34, p = 0.042), males (B = 0.31, p = 0.006), and pubertal children (B = 0.32, p = 0.046), dehydroepiandrosterone sulphate (DHEAS) showed a positive, independent association with BA SDS. No association with indicators of insulin secretion was found. Conclusion: BMI SDS is highly correlated to BA SDS in obese children. Increased DHEAS has a central role in advanced BA in obese children.

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“…Insulin is structurally analogous to IGF-1 (insulin-like growth factor 1), which binds to the IGF-1 receptor, and thus elicits similar effects on cartilage (Maor et al, 1993;Schmid, 1995;Gaissmaier et al, 2008). Insulin is structurally analogous to IGF-1 (insulin-like growth factor 1), which binds to the IGF-1 receptor, and thus elicits similar effects on cartilage (Maor et al, 1993;Schmid, 1995;Gaissmaier et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Chitosan‐based injectable hydrogel as a promising in situ forming scaffold for cartilage tissue engineering

Naderi‐Meshkin

Andreas

Matin

et al. 2013

Cell Biology International

123

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Chitosan-beta glycerophosphate-hydroxyethyl cellulose (CH-GP-HEC) is a biocompatible and biodegradable scaffold exhibiting a sol-gel transition at 37°C. Chondrogenic factors or mesenchymal stem cells (MSCs) can be included in the CH-GP-HEC, and injected into the site of injury to fill the cartilage tissue defects with minimal invasion and pain. The possible impact of the injectable CH-GP-HEC on the viability of the encapsulated MSCs was assessed by propidium iodide-fluorescein diacetate staining. Proliferation of the human and rat MSCs was also determined by MTS assay on days 0, 7, 14 and 28 after encapsulation. To investigate the potential application of CH-GP-HEC as a drug delivery device, the in vitro release profile of insulin was quantified by QuantiPro-BCA™ protein assay. Chondrogenic differentiation capacity of the encapsulated human MSCs (hMSCs) was also determined after induction of differentiation with transforming growth factor β3. MSCs have very good survival and proliferative rates within CH-GP-HEC hydrogel during the 28-day investigation. A sustained release of insulin occurred over 8 days. The CH-GP-HEC hydrogel also provided suitable conditions for chondrogenic differentiation of the encapsulated hMSCs. In conclusion, the high potential of CH-GP-HEC as an injectable hydrogel for cartilage tissue engineering is emphasised.

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Insulin enhances the growth of cartilage in organ and tissue cultures of mouse neonatal mandibular condyle

Cited by 37 publications

References 38 publications

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation

Determinants of Advanced Bone Age in Childhood Obesity

Chitosan‐based injectable hydrogel as a promising in situ forming scaffold for cartilage tissue engineering

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