Faculty / Advisor: Daniell, Henry
University of Pennsylvania School of Dental Medicine, Department of Basic and Translational Sciences
The growth hormone/insulin-like growth factor (GH/IGF) axis plays important roles in bone formation. Weaknesses in this system have been shown to result in the development of osteoporosis and other diseases of low bone mass. There is a complex set of systemic and local hormones that control this axis at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. Understanding this axis and the way it is regulated is important as it will help create useful treatments for the prevention and diseases of skeletal development and maintenance, such as osteoporosis. Bone remodeling involves the complex and coordinated interactions between the osteoblast lineage cells, which form bone, and the osteoclast lineage cells, which resorb bone. This process occurs throughout the lifespan and involves a myriad of local and systemic factors. One of the important factors that participate in bone remodeling is the growth hormone/insulin-like growth factor-I (GH/IGF) axis. The GH/GFI axis is composed of a growth hormone (GH), which is a single-chain polypeptide hormone secreted in a pulsatile manner by the anterior pituitary gland in response to hypothalamic stimulation by growth hormone releasing hormone (GHRH) and inhibition by somatostatin (SS).1 GH can directly affect cells of various tissues, including osteoclasts and epiphyseal growth-plate chondrocytes, however the way that it stimulates longitudinal bone growth is by activating hepatic IGF-I production. Other components of the GH/IGF axis include IGF-I and IGF-II, which are small peptide hormones with structures similar to insulin.3 IGF-II plays an important role in intrauterine growth while IGF-I regulates skeletal growth and maintenance during postnatal life. IGFs perform endocrine actions through circulation, but also perform local actions in an autocrine and paracrine manner.4 The systemic circulating IGF-I is secreted from the GH-induced hepatic while IGF-I production is controlled by a countless number of interactive endocrine and local signals, some of which are GH-independent.5 As a whole, the GH/IGF axis controls both, longitudinal bone growth which is important during childhood, and appositional bone growth, which is important for bone maintenance in adulthood. This presentation focuses on examining the roles of the GH/IGF axis in bone remodeling. It is the hope that this information will be used in the future for potential GH/IGF-based therapies to treat and prevent low bone mass diseases such as osteoporosis.Methods
As this was a virtual review paper, an electronic literature search was conducted in PubMed and PubMed Central databases for the following Mesh and free text terms "IGF-1", "Insulin", "bone remodeling", "Skeletal muscle", "diabetes", "periodontal diseases", "cancer" "muscle atrophy", "Duchenne muscular dystrophy", "neurodegeneration" from January 1st 1989 to July 1st 2020. Articles in English language only were included in this search.Results
The initial search in databases found 3489 hits. After removal of duplicates, 2108 articles remained for initial screening, out of these 109 articles were selected for detail inspection. Based on the pre-decided inclusion criteria, 56 studies were found eligible for participation in this study. Full text of the included studies was retrieved by electronic search from the library at Penn Dental Medicine.Conclusion
The GH/IGF axis is regulated by a multitude of interacting mechanisms and factors, particularly as it participates in the regulation of skeletal growth and maintenance. The loss of bone mass that occurs with age is in part caused by a decrease in the components involved in the GH/IGF system. Thus, GH and iGF-I therapies for the treatment of low bone mass related diseases show great promises. A better understanding of the GH/IGF axis will allow better and greater pharmacological manipulation of the physiological changes involved in low bone mass diseases and help treat those debilitating conditions.