Understanding developmental mechanisms in the context of osteoarthritis.

Osteoarthritis (OA) is a joint disease that is highly related to aging. However, as OA development is the consequence of interplay between external stimuli, such as mechanical loading and the structure and physiology of the joint, it can be anticipated that variation in developmental processes early in life will affect OA development later in life. Genes involved in patterning processes, such as the Hox genes, but also genes that encode transcription factors, growth factors and cytokines and their respective receptors and those that encode molecules involved in formation of the extracellular matrix, will influence embryonic skeletal development and OA incidence and severity in the adult. The function of genes involved in patterning processes can be partly be understood by close analysis of inborn diseases that result in musculoskeletal syndromes, but a deeper understanding will be the result of specific gene knockouts or overexpression in transgenic mouse models.