DKK1 is both anabolic and anticatabolic in bone. TNF-α enhances DKK1 secretion which inhibits MSC-derived osteoblastogenesis and lowers OPG levels, resulting in reduced bone accretion. In addition, DKK1 enhances RANKL levels, and the increased RANKL:OPG ratio activates osteoclast activity, leading to bone resorption.