Figure 1.

Role of CCL2 in PTH/PTHrP Action on Bone Cells. Osteoclasts are large, multinucleated cells formed from the fusion of mononuclear progenitors of the monocyte/macrophage lineage. However, osteoblasts originate from mesenchymal stem cells. In the process of bone remodeling, both osteoblasts and osteoclasts are highly dependent on one another to sustain normal bone mass. Osteoblasts secrete CCL2 on binding parathyroid hormone (PTH) to its receptor parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R), which is present on the osteoblast. PTH-induced CCL2 facilitates the recruitment of monocytes and preosteoclasts to remodeling sites. At the same time, CCL2 also participates in the fusion of preosteoclasts to mature osteoclasts. The transient increase in CCL2 expression and resultant osteoclast activity is required for the anabolic effect of PTH on bone. Tumor cells produce parathyroid hormone-related peptide (PTHrP), which stimulates CCL2 expression from bone-forming osteoblasts. Osteoblastic CCL2 increases osteoclastogenesis and bone resorption to facilitate tumor growth in bone.