Biology of the basic multicellular unit and the pathophysiology of osteoporosis.
Bone structural integrity is maintained by removal of old bone by osteoclasts and synthesis of new bone in its place by osteoblasts. This process, called bone remodeling, is accomplished by assembly of osteoclasts and osteoblasts into discrete temporary anatomic structures called basic multicellular units (BMUs). The lifespan of osteoclasts and osteoblasts is short compared to the lifespan of the BMU; therefore, they must be continually replenished for BMU progression to occur. Osteoclasts develop from hematopoeitic progenitors; and osteoblasts are derived from mesenchymal stem cells, also known as marrow stromal fibroblasts. Circulating hormones together with locally produced cytokines and growth factors modulate the replication and differentiation of osteoclast and osteoblast progenitors. The most important locally produced pro-osteoclastogenic cytokine is receptor activator of NF-kappaB (RANK) ligand. It is expressed by stromal/osteoblastic cells, and binds to its receptor (RANK) on osteoclast progenitors to stimulate differentiation. The development of mature osteoblasts is promoted by growth factors released from the bone matrix during resorption, as well as by growth factors produced by osteoblast progenitors themselves. Many of these same locally produced factors and cytokines also govern the lifespan of osteoclasts and osteoblasts by their effects on apoptosis. The orderly genesis and apoptosis of both osteoclasts and osteoblasts is essential for normal bone homeostasis during bone remodeling. Bone loss caused by sex steroid deficiency or glucocorticoid excess is caused by alteration of bone cell production, and by prolonging osteoclast lifespan and shortening osteoblast lifespan. Therapies that prevent or reverse osteoporosis act at least in part by preventing osteoblast apoptosis and/or stimulating osteoclast apoptosis.
Jilka
Robert L
RL
Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. rljilka@life.uams.edu
D000818:Animals; D001853:Bone Marrow / Q000503:physiopathology*; D016723:Bone Remodeling; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010024:Osteoporosis / Q000503:physiopathology*
D016207:Cytokines