Advances in osteoclast biology: old findings and new insights from mouse models

Abstract

The maintenance of adequate bone mass is dependent upon the controlled and timely removal of old, damaged bone. This complex process is performed by the highly specialized, multinucleated osteoclast. Over the past 15 years, a detailed picture has emerged describing the origins, differentiation pathways and activation stages that contribute to normal osteoclast function. This information has primarily been obtained by the development and skeletal analysis of genetically modified mouse models. Mice harboring mutations in specific genetic loci exhibit bone defects as a direct result of aberrations in normal osteoclast recruitment, formation or function. These findings include the identification of the RANK-RANKL-OPG system as a primary mediator of osteoclastogenesis, the characterization of ion transport and cellular attachment mechanisms and the recognition that matrix-degrading enzymes are essential components of resorptive activity. This Review focuses on the principal observations in osteoclast biology derived from genetic mouse models, and highlights emerging concepts that describe how the osteoclast is thought to contribute to the maintenance of adequate bone mass and integrity throughout life.

The vacuolar-type H+-ATPase at a glance – more than a proton pump

“…Osteoclasts are large multinucleated cells of the monocyte family that function in bone remodeling (Edwards and Mundy, 2011;Teitelbaum and Ross, 2003). When not resorbing bone tissue, osteoclasts contain many intracellular vesicles that are rich in V-ATPases.…”

R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts

“…Osteoclasts are multinucleated giant cells responsible for bone resorption (Edwards and Mundy 2011). It is generally accepted that osteoblasts control osteoclast differentiation and bone-resorbing activity through cell-cell physical contact (Takahashi et al 1988;Takami et al 1999).…”

“…Osteoblasts produce a membranebound cytokine known as receptor activator of NF-jB ligand (RANKL) that triggers osteoclast differentiation from osteoclast precursors in the presence of macrophage colony-stimulating factor (M-CSF) (Edwards and Mundy 2011). A receptor for RANKL, termed RANK, is expressed on osteoclast precursors and activates intracellular signaling pathways, which regulate the expressions of genes related to osteoclastogenesis (Edwards and Mundy 2011).…”

Dual effects of baicalin on osteoclast differentiation and bone resorption

“…Together with osteoblasts and osteocytes, osteoclasts play a prominent role in bone homeostasis 3, 4, 5. Many bone diseases are caused by disorders of osteoclast differentiation and function.…”