Role of insulin‐like growth factors (IGFs), their receptors and genetic regulation in the chondrogenesis and growth of the mandibular condylar cartilage

Abstract

Growth of the mandibular condylar cartilage (MCC) is reviewed as a function of genetic and epigenetic factors. The growth centers around the differential spatial concentration of the chondrocytes, influence of growth factors like TGF-β and heterogeneity in the number of IGF receptors, control the action of IGF. Besides these factors, growth of the mandibular condyle is influenced by differential response of chondrocytes as a function of their source/ageing, which in turn is regulated by TGF-β, BMPs and IGFs. While IGF-1 promotes proteoglycan synthesis and survival of the chondrocytes to maintain cartilage homeostasis, TGF-β synergistically catalysed the effect of IGF-1, while BMPs catalysed proteolysis as and when physiologically needed. To understand these processes, role of IGF-1 and its six receptors is at the center to a number of physiological processes being regulated by its mode of application for the growth and differentiation. Probing deeper, biological functions of IGFs seemed to depend on their level of free status rather than bound status to respective IGF-binding proteins (IGF-BPs), considered prerequisite to modulate their biological functions. Genetic regulation of their secretion has thrown light on their insulin-like structural homology, level and response in osteo-arthritis (OA), rheumatic arthritis (RA) and diabetes type-II. Biochemistry and spatial distribution of IGF receptors in different domains exerts control on IGF-1 activities. In ultimate analysis, IGF-axis conserved during the evolution to regulate cell growth and proliferation affect nearly every organ in the body as judged from the techniques determining skeletal maturity and decision making dependent on it for orthodontic, orthognathic/orthopedic and dental implant applications.

Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer

“…IGF-1 modulates MSC chondrogenesis by stimulating and increasing cell proliferation, regulates cell apoptosis, and induces in vitro expression of chondrocyte markers as proteoglycans and COL II [35,36]. IGF-1 has also been shown to improve chondrogenesis by increasing COL II and AGC expression when given in combination with TGF-β1, bone morphogenic protein-6 and TGF-β3 [12,37,38], but when administered alone is not sufficiently inductive in MSCs [39-41] or in ASCs, where exogenous protein was necessary in greater doses [42].…”

Genetic expression of MMP-Matrix-mettalo-proteinases (MMP-1 and MMP-13) as a function of anterior mandibular repositioning appliance on the growth of mandibular condylar cartilage with and without administration of Insulin like growth factor (IGF-1) and Transforming growth factor-B (TGF-β)

“…S. In totality, these observations on the young rabbits reflected condylar growth, confirming earlier observations on mice and rats that IGF-1 and TGF-b complement the growth of MCC vascular endothelial growth factor. 6,14,15 The growth of the mandibular cartilage was evident by an increase in the length of the cartilage and an increase in the proliferative layer of the cartilage as shown in Figure 3 in the descending order AI . AS .…”

HIF-1α as a Regulator of BMP2-Induced Chondrogenic Differentiation, Osteogenic Differentiation, and Endochondral Ossification in Stem Cells

“…However, the successful generation of stable hyaline cartilage tissue using MSCs requires the efficient delivery of the factors stimulating chondrogenesis [1,15]. Many studies have reported that certain growth factors, such as transforming growth factor (TGF)-βs [16,17], bone morphogenetic proteins (BMPs) [18,19], fibroblast growth factors (FGFs) [20], and insulin-like growth factor (IGF)-1 [21,22], are capable of directing MSCs to chondrocyte phenotypes. However, these growth factors have not been extensively used due to their limited abilities to synthesize specific cartilage matrix components.…”