Matrix metalloproteinases and their inhibitors in bone: an overview of regulation and functions.

Matrix metalloproteinases (MMPs), a family of Zn2+-dependent endopeptidases, mediate different physiological processes by digesting components of the extracellular matrix. Nevertheless, overexpression of MMPs is implicated in the pathogenesis of various diseases. Different MMPs and tissue inhibitors of MMPs (TIMPs) are expressed in bone cells, and their biosynthesis is regulated by local and systemic hormones and factors. The levels of enzymatically active MMPs in bone are further controlled by secretion, activation of proenzymes, inhibition by TIMPs, cellular uptake and degradation. Members of the cysteine and serine family of proteinases also coordinate some of the biological activities of MMPs in bone. The functions of MMPs and TIMPs in bone include regulation of processes, such as degradation of collagen and other components of the bone matrix, migration and survival of bone cells, endochondral bone formation and bone resorption. Abnormal expression of MMPs may lead to pathological conditions affecting bone and cartilage. Various pharmacological agents can inhibit MMPs, and some of these inhibitors may be potential therapeutic agents for certain bone diseases. This review briefly describes the regulation and functions of different MMPs and TIMPs in bone, and provides an insight into the role of MMPs in bone development, remodeling and pathology.