Gnawing at the bone

杨柳

The destructive ability of osteoclasts (OCs) to weaken bones is reduced by the interaction between an extracellular matrix (ECM) ligand and an adhesion receptor, according to results from Spessotto et al. on page 1133.) U  U3 L) }2 I3 _* [0 x; F4 K
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The correct balance between bone-destroying OCs and bone- generating osteoblasts maintains bone mass in adults. However, too much OC activity can cause diseases like osteoporosis and rheumatoid arthritis. OCs are derived from hematopoietic precursors that leave the bloodstream and migrate toward the bone surface. Once they reach their destination, the precursors stop migrating and differentiate into OCs, which secrete cysteine proteases that chew up the bone.& Y9 x% V4 E7 p  U6 R( o2 c

+ P9 n. l! ^4 q+ P2 QOther proteases, namely matrix metalloproteases (MMPs), are thought to help mobilize OCs by degrading small pieces of the ECM. As such, Spessotto et al. were not surprised to find that reducing MMP-9 expression in OCs led to a shift from OC migration to adherence.# x$ I# v+ S. Z7 L2 ]( R$ T
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What they did not anticipate was what causes MMP-9 inhibition in vivo. MMP-9 expression was reduced and migration ceased when cells encountered hyaluronic acid (HA), an ECM component. The cells bind HA via CD44, and this engagement normally promotes cell motility, as seen in melanoma cells. But OCs migrating in vitro on various other ECM components, including laminin and fibronectin, stopped when they encountered HA. They also stopped when MMP-9 activity was inhibited, either chemically or using antisense techniques. The group does not yet know how HA binding elicits MMP-9 down-regulation, but they have initial evidence that HA also inhibits motility in certain tumor cells.(OCs adhere when HA/CD44 binding inhibits)