Matrix metalloproteinases in bone health and disease

Abstract

During bone development the extracellular matrix (ECM) undergoes extensive modeling and remodeling by different proteases including members of the matrix metalloproteinase (MMP) family. The most dominant MMPs in bone development are the gelatinases MMP-2 and MMP-9, the collagenase MMP-13 and the membrane-bound MT1-MMP. The enzymes are secreted by different cells in the bone microenvironment, including osteocytes, osteoblasts, osteoclasts, chondrocytes, and endothelial cells. In endochondral bone development, MMPs are involved as early as the initial vascularization of the cartilage anlage while later they regulate chondrocytes proliferation, differentiation, and apoptosis at the growth-plate, as well as vascularization at the chondro-osseous junction. At sites of bone resorption the relative importance of MMPs for matrix degradation depends on the bone type: they participate in resorption of calvarial but not long bones while in the latter they are significant for osteoclasts migration and invasion. The importance of MMPs in bone development is emphasized by several bone-related syndromes in human with single mutations in MMP genes. These, together with targeted mutation in animal models shed light on the role of different MMPs in many aspects of bone development. In this view it is not surprising that MMPs also participate in pathological conditions in bones. They play significant role in migration and establishment of tumor metastasis into bone and tumor-induced osteolysis; they are dominant in the degradation of collagen type I during the course of osteoarthritis; and are even involved in fracture repair. In this chapter we summarize the current knowledge regarding the central role of MMPs in bone health and disease.