Role of Proteases in Osteoclastic Resorption

Abstract

This chapter discusses the role of proteases in osteoclastic resorption. Major constituents of bone matrix are type I collagen and a basic calcium salt. Degradation of the bone collagen, as well as bone mineral solubilization, is the processes through which osteoclasts resorb bone. For the degradation of collagen, osteoclasts produce several kinds of proteases, including matrix metalloproteinases (MMPs) and cathepsins. Several cysteine proteases and a few aspartic and serine proteases are present ubiquitously in lysosomes of various mammalian cells and serve as scavengers that degrade denatured, unnecessary, or harmful proteins. The involvement of cysteine proteases in bone resorption has been also suggested by in vivo studies. The intraperitoneal injection of leupeptin or E-64 in rats caused a fall in serum calcium and urinary excretion of hydroxyproline. Taken together, the in vitro and in vivo studies stress even more strongly that cysteine proteases play a key role in the osteoclastic bone resorption. The chapter concludes that both MMPs and lysosomal cysteine proteinases, most probably MMP-9 and cathepsin K, are likely to be responsible for bone matrix degradation.