Attachment of the osteoclast to the osteon begins the process. This is associated with an increase in osteoclast activity. Note that these molecules also regulate differentiation of the osteoclast. It is proposed that CCL2 and RANTES act as autocrine loop in human osteoclast differentiation. Recent research indicates that calcitriol leads to a reduction in osteoclast formation, and bone resorption. Bone erosion caused by mature osteoclast cells is common in patients with rheumatoid arthritis. MMPs expressed by the osteoclast include MMP-9, -10, -12, and -14. This protein functions as an autocrine factor which heightens osteoclast formation and bone resorption. In knockout studies, TRAP mice exhibit mild osteopetrosis, associated with reduced osteoclast activity. Osteoprotegerin is secreted by osteoblasts and is able to bind RANK-L, inhibiting osteoclast stimulation. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. At the same time, it has a direct effect on osteoclast activity. These bacteria are not mediators of osteoclast activity but do cause leukocyte chemotaxis. In space, however, there is an increase in osteoclast activity due to microgravity. With the sealing zone in place, the multinucleated osteoclast reorganizes itself.