Bone

Osteoclast differentiation

Osteoblast VS Osteoclast

Osteoblasts are cells with a single nucleus that arise from mesenchymal stem cells found in the periosteum and bone marrow.

In contrast, osteoclasts originate from the mononuclear phagocytic cell lineage and are ultimately formed when several precursor cells fuse to create a multinucleated mature cell.

The 2 most important factors for osteoclastic differentiation, macrophage colony-stimulating factor (M-CSF) and receptor for activated nuclear factor kappa-B ligan (RANK-L), are produced by osteoblasts and bone marrow stromal cells.

Osteoprotegerin (OPG) is a physiologic decoy receptor that decreases binding of RANK-L to RANK.

Inhibition of that --> reduces the differentiation and survival of osteoclasts --> decreased bone resorption and increased bone density.

OPG loss-of-function mutations cause juvenile Paget's disease.

A monoclonal antibody (denosumab) that inhibits the RANK/RANK-L interaction also leads to increased bone density and is commonly used for the treatment of osteoporosis.

TGF-beta increases the replication of osteoblast precursors, leading to increased formation of mature osteoblasts. It also increases collagen synthesis and decreases bone resorption by increasing osteoclastic apoptosis.