Impaired growth plate chondrogenesis in children with chronic illnesses

In mammals, statural growth is primarily accomplished by endochondral ossification, which takes place at the growth plate. Growth plate chondrocyte proliferation, hypertrophy/differentiation, apoptosis, and cartilage matrix synthesis all contribute to chondrogenesis or cartilage formation, a process tightly coupled to the simultaneous remodeling of the cartilage into bone at the metaphyseal border of the growth plate. Growth plate chondrogenesis is regulated by the complex interaction of molecular signals acting systemically as well locally within the growth plate. This network is often dysregulated during chronic illnesses, thus resulting in impaired growth plate chondrogenesis and, in turn, growth failure. The principal events responsible for altered growth plate chondrogenesis in chronic illness are inflammation, protein/calorie deprivation, uremia/metabolic acidosis, glucocorticoids, and impaired GH/IGF-I axis.