The osteoclasts intervened by knock-down angiopoietin-like protein2 could promote expressions of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, and CCL-2, reduce Runx2, OPN, and Colla1 levels, finally improve bone loss and BMD in osteoporosis mice induced by ovariectomy (59). The gene discussed is SPP1; the disease is osteoporosis.