The Actions of IGF-1 in the Growth Plate and Its Role in Postnatal Bone Elongation

Racine, Holly; Serrat, Maria A.

doi:10.1007/s11914-020-00570-x

Cited by 56 publications

(42 citation statements)

References 231 publications

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“…A 3‐year follow‐up study demonstrated that IGF‐1 levels significantly positively associated with the BMD at both baseline and follow‐up 23 . Recently, the review articles revealed that the BMD and bone elongation increased by the actions of IGF‐1 on skeletal acquisition through stimulation of extracellular matrix production and growth plate through regulation of cell proliferation and differentiation 24,25 . In this study, there was positively significant correlation between the serum IGF‐1 and ALP levels in healthy population, but negative correlation was found between serum IGF‐1 and AST levels even though the correlation was not statistical significance.…”

Section: Discussionmentioning

confidence: 49%

Insulin‐like growth factor‐1 positively associated with bone formation markers and creatine kinase in adults with general physical activity

Lee

Hsiao

Yang

et al. 2021

Clinical Laboratory Analysis

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Background The Insulin‐like growth factor‐1 (IGF‐1) is primarily synthesized by hepatocytes in a growth hormone (GH)‐dependent manner, it is also produced by bone and muscle. The effects of exercise on the associations between IGF‐1 levels and bone turnover markers (BTM) were found in the previous studies. However, the associations between the levels of IGF‐1 and BTM, liver function tests, and skeletal muscle markers in adults with general physical activity were not clear. Methods Ninety‐four participants were recruited from healthy survey. Blood samples were collected to analyze the levels of IGF‐1, total protein (TP), albumin (Alb), total bilirubin (T‐Bil), direct bilirubin (D‐Bil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine (CRTN), and glucose. Urine samples were collected to analyze the CRTN and deoxypyridinoline (Dpd) levels. Results The positively significant associations were found between the IGF‐1 levels and the levels of ALP, BALP, and CK, respectively. No significant associations were found between the IGF‐1 levels and the levels of TP, Alb, A/G, T‐Bil, D‐Bil, AST, ALT, LDH, glucose, urinary CRTN, urinary Dpd, and Dpd/CRTN ratios, respectively. Conclusion The serum IGF‐1 levels associated with the levels of skeletal muscle and bone formation markers (BFM), not the bone resorption markers under general physical activity in the healthy adults. The physician needs to consider the effects of bone formation and skeletal muscle markers on the IGF‐1 levels in the management of IGF‐1‐related disorders.

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Section: Discussionmentioning

confidence: 49%

Insulin‐like growth factor‐1 positively associated with bone formation markers and creatine kinase in adults with general physical activity

Lee

Hsiao

Yang

et al. 2021

Clinical Laboratory Analysis

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“…BMP-5 and BMP-6 induce the formation of cartilage and bone in the rat subcutaneous transplant model, but the former requires higher doses for similar osteoinduction [31]. IGF-1 regulates bone length of the skeleton acting on chondrocytes of the proliferative and hypertrophic zones of the growth plate [8,54,55].…”

Section: Discussionmentioning

confidence: 99%

Growth factors in the initial stage of bone formation, analysis of their expression in chondrocytes from epiphyseal cartilage of rat costochondral junction

Hyc

Moskalewski

Osiecka-Iwan

2021

Folia Histochem Cytobiol.

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“…It is generally accepted that GH and IGF-1 are the main primary drivers of length growth [84][85][86] but in the foetus and early infancy, GH may be much less involved, with IGF-1 and insulin playing the major role. In the Karlberg infancy-childhood-puberty (ICP) growth model of three additive and partly superimposed components of linear growth, this infancy component is proposed to last for about 10 months [11,87,88].…”

Section: Endocrine Regulation Of Statural Growthmentioning

confidence: 99%

“…IGF-1 is expressed in tissues throughout the body and its role in height growth is likely mediated mainly through paracrine/autocrine mechanisms within the growth plate [84,86]. However, in IGF-1 transgenic mice, which overexpress the hepatic IGF-1 gene with high levels of serum IGF-1, weight and length growth is either increased in otherwise normal mice (which express growth plate IGF-1), or normalised in IGF-1 KO mice (apart from some early postnatal skeletal growth slowing) [96].…”

Section: Endocrine Regulation Of Statural Growthmentioning

confidence: 99%

“…While the endocrine anabolic influences of GH and IGF-1 [86] and thyroid hormones [107] and the local paracrine/autocrine influences on endochondral ossification are relatively well understood, as discussed elsewhere [120], the extent and nature of direct anabolic influences of amino acids and important regulatory cations like Zn 2+ on endochondral ossification are poorly understood. However, chondrocyte development in cell culture is sensitive to amino acid levels [121], length growth in vivo in rodent models is extremely sensitive to dietary protein intake, and given the importance of mTORC1 for bone growth [122][123][124]) and for the coordination of chondrocyte proliferation and hypertrophy [78] as shown in Figure 2, there is no reason not to believe that amino acids activate it as identified in other tissues.…”

Section: Endochondral Ossificationmentioning

confidence: 99%

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Interactions between Growth of Muscle and Stature: Mechanisms Involved and Their Nutritional Sensitivity to Dietary Protein: The Protein-Stat Revisited

Millward

2021

Nutrients

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Childhood growth and its sensitivity to dietary protein is reviewed within a Protein-Stat model of growth regulation. The coordination of growth of muscle and stature is a combination of genetic programming, and of two-way mechanical interactions involving the mechanotransduction of muscle growth through stretching by bone length growth, the core Protein-Stat feature, and the strengthening of bone through muscle contraction via the mechanostat. Thus, growth in bone length is the initiating event and this is always observed. Endocrine and cellular mechanisms of growth in stature are reviewed in terms of the growth hormone-insulin like growth factor-1 (GH-IGF-1) and thyroid axes and the sex hormones, which together mediate endochondral ossification in the growth plate and bone lengthening. Cellular mechanisms of muscle growth during development are then reviewed identifying (a) the difficulties posed by the need to maintain its ultrastructure during myofibre hypertrophy within the extracellular matrix and the concept of muscle as concentric “bags” allowing growth to be conceived as bag enlargement and filling, (b) the cellular and molecular mechanisms involved in the mechanotransduction of satellite and mesenchymal stromal cells, to enable both connective tissue remodelling and provision of new myonuclei to aid myofibre hypertrophy and (c) the implications of myofibre hypertrophy for protein turnover within the myonuclear domain. Experimental data from rodent and avian animal models illustrate likely changes in DNA domain size and protein turnover during developmental and stretch-induced muscle growth and between different muscle fibre types. Growth of muscle in male rats during adulthood suggests that “bag enlargement” is achieved mainly through the action of mesenchymal stromal cells. Current understanding of the nutritional regulation of protein deposition in muscle, deriving from experimental studies in animals and human adults, is reviewed, identifying regulation by amino acids, insulin and myofibre volume changes acting to increase both ribosomal capacity and efficiency of muscle protein synthesis via the mechanistic target of rapamycin complex 1 (mTORC1) and the phenomenon of a “bag-full” inhibitory signal has been identified in human skeletal muscle. The final section deals with the nutritional sensitivity of growth of muscle and stature to dietary protein in children. Growth in length/height as a function of dietary protein intake is described in the context of the breastfed child as the normative growth model, and the “Early Protein Hypothesis” linking high protein intakes in infancy to later adiposity. The extensive paediatric studies on serum IGF-1 and child growth are reviewed but their clinical relevance is of limited value for understanding growth regulation; a role in energy metabolism and homeostasis, acting with insulin to mediate adiposity, is probably more important. Information on the influence of dietary protein on muscle mass per se as opposed to lean body mass is limited but suggests that increased protein intake in children is unable to promote muscle growth in excess of that linked to genotypic growth in length/height. One possible exception is milk protein intake, which cohort and cross-cultural studies suggest can increase height and associated muscle growth, although such effects have yet to be demonstrated by randomised controlled trials.

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The Actions of IGF-1 in the Growth Plate and Its Role in Postnatal Bone Elongation

Cited by 56 publications

References 231 publications

Insulin‐like growth factor‐1 positively associated with bone formation markers and creatine kinase in adults with general physical activity

Insulin‐like growth factor‐1 positively associated with bone formation markers and creatine kinase in adults with general physical activity

Growth factors in the initial stage of bone formation, analysis of their expression in chondrocytes from epiphyseal cartilage of rat costochondral junction

Interactions between Growth of Muscle and Stature: Mechanisms Involved and Their Nutritional Sensitivity to Dietary Protein: The Protein-Stat Revisited

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