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Anatomy, physiology and disease
Published in C M Langton, C F Njeh, The Physical Measurement of Bone, 2016
Although it is beyond the scope of this chapter to discuss in detail all metabolic bone diseases, it should be quite apparent that skeletal disorders can affect any or all of the three major components of bone substance, i.e. bone cells, matrix or mineral. As noted above, mineralization defects define the osteomalacia syndrome. Numerous diseases target bone cells and there are primary and secondary collagen disorders which can affect the quality and quantity of bone matrix. Mutations in specific growth factors or cytokines can have a profound effect on the skeleton of mammals. For example, a deletion of the gene encoding mCSF results in severe and potentially lethal osteopetrosis due to the absence of osteoclasts [16]. Mice with an induced Cbfal knock-out are completely lacking in new bone [29]. A deletion in exon 5 of the IGF-I gene leads to low bone density and failure to grow. Despite this ever-growing list, it is clear that the majority of individuals who suffer from the number one cause of metabolic bone disease, i.e. osteoporosis, do not have single mutations but rather have impairment in peak bone mass as a result of polygenic influences and environmental interactions.
Medium Design for Cell Culture Processing
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
Insulin plays a key role in regulating glucose uptake for many cell types. In addition to modulating glucose metabolism, insulin also exhibits mitogenic effects and stimulates cell growth through an overlapping pathway with IGF-1 (Panel 7.25). IGF-1 has an acute effect on protein and carbohydrate anabolism by increasing cellular uptake of amino acids and glucose, and by stimulating glycogen and protein synthesis. IGF-1 also affects cell proliferation, differentiation, and apoptosis. It is a potent mitogen that increases DNA synthesis and stimulates the expression of cyclin D in a wide variety of cells.
European regulatory guidance
Published in Sarfaraz K. Niazi, Biosimilars and Interchangeable Biologics, 2016
Growth hormone has potent anabolic, lipolytic, and anti-insulin effects (acute insulin-like effect). The effects of GH are mediated both directly (e.g., on adipocytes and hepatocytes) and indirectly via stimulation of insulin-like growth factors (principally IGF-1). Somatropin-containing medicinal products are currently licensed for normalizing or improving linear growth and/or body composition in GH-deficient and certain non-GH-deficient states. The same receptors are thought to be involved in all currently approved therapeutic indications of rhGHs.
Dynamical release nanospheres containing cell growth factor from biopolymer hydrogel via reversible covalent conjugation
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Bowen Ren, Xueyun Chen, Ye Ma, Shoukang Du, Saibo Qian, Yongjie Xu, Zhilin Yan, Jianliang Li, Yang Jia, Huaping Tan, Zhonghua Ling, Yong Chen, Xiaohong Hu
HP-maltose and HP-PBA were characterized by 1H NMR measurement (Figure 2(a)). As shown in spectrum of HP-maltose, the peaks at 3.1–3.7 ppm were due to the –CH protons of maltose. In spectrum of HP-PBA, the peak at 7.4 ppm is assigned to –CH protons of PBA. The NS were prepared by cross-linking HP-maltose via the inverse emulsion cross-linking technique. To demonstrate the affinity delivery of cell growth factors, HP-maltose NS were employed as the IGF-1 carrier. The NS with controlled particle size were generated when the cross-linking was carried out within the micro-emulsions. Based on our previous optimization of the polymer concentration, the number-averaged size of NS was 550 nm with 2.0 wt% of HP-maltose after IGF-1 encapsulation (Figure 2(b)). As shown in the SEM inset of Figure 2(b), the NS were well-defined spheres with smooth surfaces irrespective of the maltose content in the composition. The SEM result showed a slightly smaller number-averaged diameter than the hydrodynamic size of IGF-1 loaded NS. Encapsulated IGF-1 was verified by the enzyme-linked immunosorbent assay (ELISA). According to immunoassay measurement, the NS showed an encapsulation of 23.5 ng of IGF-1 per mg of NS, giving an entrapment of 41.4%. The synthesis of heparin derivatives and hydrogel was confirmed by FT-IR measurements. Figure 2(c) displayed FT-IR spectra of the HP-maltose, HP-PBA and cross-linked hydrogel. Analysis of HP-maltose and HP-PBA spectra revealed C=O and boronate peaks at 1454 and 1466 cm−1 corresponding to the maltose on HP-maltose and the PBA on HP-PBA, respectively. The cross-linked hydrogel spectrum showed increased absorption indicating the consumption of individual maltose and PBA groups and the formation of a boronate–maltose adduct during the reaction.
Embryonic arsenic exposure reduces intestinal cell proliferation and alters hepatic IGF mRNA expression in killifish (Fundulus heteroclitus)
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Kaleigh C. Sims, Katey L. Schwendinger, Dana B. Szymkowicz, Jonathan R. Swetenberg, Lisa J. Bain
IGF-1 is an important growth signal in both mammals and fish (Bower and Johnston 2010; Reindl et al. 2011). Hepatic IGF-1 protein production is stimulated by growth hormone via the JAK/STAT pathway (Vélez et al. 2018) and secreted into the bloodstream where it binds IGF-1 receptors (IGF-1R) on cells such as skeletal myocytes. The binding activates the PI3K-AKT-TOR signaling pathway to enhance the expression of genes such as myogenin, PCNA, and myostatin, thereby increasing skeletal muscle proliferation and differentiation (Fuentes et al. 2013; Rechler and Clemmons 1998).
Low energy availability in female athletes: From the lab to the field
Published in European Journal of Sport Science, 2022
Ida A. Heikura, Trent Stellingwerff, Jose L. Areta
Insulin-like growth factor 1 (IGF-1) and growth hormone (GH). IGF-1 is an important hormone for protein synthesis and cell proliferation (Clemmons, 2009). Pituitary release of GH exerts the majority of its effects through regulating IGF-1 release from the liver (Fazeli & Klibanski, 2014). LEA induces a state of GH resistance, in which normal GH effect on liver IGF-1 release is impaired, resulting in increased circulating GH and reduced circulating IGF-1 (Fazeli & Klibanski, 2014). LEA induces a state of GH resistance within days, making both GH and IGF-1 good candidates as clinical markers of short-term LEA. Three studies in females have reported GH concentrations above resting levels with 4–5 days of EA ≤20 kcal/kg FFM/d (Loucks, 2006; Loucks & Thuma, 2003; Loucks et al., 1998). The 24 h average GH concentration has been shown to increase by 23–120% with an EA of 10–20 kcal/kg FFM/d (Loucks, 2006; Loucks & Thuma, 2003), while morning values increased by ∼26% with an EA ∼13 kcal/kg FFM/d (Loucks et al., 1998), with no effect with an EA of 30 kcal/kg FFM/d (Loucks, 2006; Loucks & Thuma, 2003). IGF-1 has been shown to consistently be reduced with similar amounts of LEA in studies with female participants (Loucks, 2006; Loucks & Heath, 1994a; Loucks & Thuma, 2003; Loucks et al., 1998; Papageorgiou, 2017, 2018). The reduction of morning circulating IGF-1 values has been on average ∼34% for short-term EA 10–20 kcal/kg FFM/d (Loucks, 2006; Loucks & Heath, 1994a; Loucks & Thuma, 2003; Loucks et al., 1998; Papageorgiou, 2018), while no effect was seen with an EA of 30 kcal/kg FFM/d (Loucks & Thuma, 2003). Based on the evidence, IGF-1 seems to have significant support to be used as a morning marker of short-term LEA, while GH is unclear. IGF-1 and GH are typically not routine tests but can be easily accessed on demand.