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Active osteoclasts (
) resorb bone (
) along the gradient (red) of the RANKL field (
), and move from left to right. The tumor (
) invades the space previously resorbed by active osteoclasts. Cancer cells produce PTHrP (
), which diffuses and induces the expression of additional RANKL by osteoblastic bone cells. Cancer cells also produce OPG (
) which diffuses, inhibits RANKL, and hence modifies the RANKL–gradient.
