Biological mechanisms of bone and cartilage remodelling--genomic perspective

Abstract

Rapid advancements in the field of genomics, enabled by the achievements of the Human Genome Project and the complete decoding of the human genome, have opened an unimaginable set of opportunities for scientists to further unveil delicate mechanisms underlying the functional homeostasis of biological systems. The trend of applying whole-genome analysis techniques has also contributed to a better understanding of physiological and pathological processes involved in homeostasis of bone and cartilage tissues. Gene expression profiling studies have yielded novel insights into the complex interplay of osteoblast and osteoclast regulation, as well as paracrine and endocrine control of bone and cartilage remodelling. Mechanisms of new bone formation responsible for fracture healing and distraction osteogenesis, as well as healing of joint cartilage defects, have also been extensively studied. Microarray experiments have been especially useful in studying pathological processes involved in diseases such as osteoporosis or bone tumours. Existing results show that microarrays hold great promise in areas such as identification of targets for novel therapies or development of new biomarkers and classifiers in skeletal diseases.

Fig. 1

Mechanisms of osteoblast and osteoclast function induced by Wnt signalling. a When the pathway is activated, osteoblasts differentiate and through mature osteoblast upregulation of OPG inhibit RANKL-induced osteoclastogenesis preventing bone resorption. b When the pathway is arrested, osteoblast proliferation and differentiation also cease, causing the precursors of mature osteoblasts to activate RANKL. Osteoclastogenesis and bone resorption follow. OPG osteoprotegerin, RANKL receptor activator of NF-κB ligand (modified from [8])