Targeting osteoclast-osteoblast communication

New bone formation occurs at bone resorption sites in each cycle of bone remodeling to maintain the microarchitecture for bone mechanical properties. It is therefore essential that bone resorption and bone formation occur at the same place but at different moments. This is achieved through different levels of cellular communication. The authors [1] review three different communication levels.

First, bone resorption allows release of molecules from the bone matrix. Release of TGF-β1 allows the recruitment of osteoblasts as it activates migration of bone marrow mesenchymal cells, the precursors of osteoblasts, to form new bone. This factor allows spatiotemporal coupling of resorption and new bone formation.

Second, osteoclast differentiation is mainly under the control of matrix bone cells, particularly the osteoblast-derived cells, osteocytes. These cells produce Receptor Activator of NF-κB Ligand (RANKL) that interacts with its receptor RANK on osteoclasts. Osteoprotegerin produced by preosteoblasts can inhibit the osteoclast differentiation by direct interaction with RANKL.

Finally, it has been recently shown that osteoclasts produce Semaphorin 4D (Sema4D) which directly regulates osteoblast differentiation and mobility via osteblast receptor Plexin B1. Osteoclast production of Sema4D is stimulated by increased osteoblastic RANKL. Sema4D then inhibits osteoblast differentiation to balance the supply of osteoclasts and osteoblasts, thus functioning in a negative-feedback loop.

1. Cao X. Nat Med. 2011;17:1344-1346