Porth's Essentials of Pathophysiology, 4e

1071

Structure and Function of the Skeletal System

C h a p t e r 4 2

Osteoblasts

Osteoid

Bone Formation. After osteo- clastic activity has ceased, osteo- blasts begin to deposit the organic matrix (osteoid) on the wall of the osteon canal. As successive lamel- lae of bone are deposited, the canal ultimately attains the relative pro- portions of the original osteon. In the formation and maintenance of bone, osteoblasts provide much of the local control because not only do they produce new bone matrix, they play an essential role in mediat- ing osteoclast activity. Many of the primary stimulators of bone resorp- tion, such as parathyroid hormone, have minimal or no direct effects on osteoclasts. Once the osteoblast, which has receptors for these sub- stances, receives the appropriate signal, it releases a soluble mediator called RANKL that induces osteo- clast activity. 3 Control of Bone Metabolism and Remodeling. The pivotal pathway linking osteoclast-mediated bone resorption with osteoblast- mediated bone formation consists of a paracrine system that includes RANKL, its receptor RANK, and a soluble protein called osteopro- tegerin (OPG). RANKL, which is produced by osteoblasts and their precursors, binds to RANK, promoting osteoclast differentia- tion and proliferation. The soluble OPG molecule, which is produced by a number of tissues, acts as a decoy receptor to block the action of RANKL. This system ensures the tight coupling of bone forma- tion and resorption, and provides a means whereby a wide variety of biologic mediators (e.g., hormones, cytokines, growth factors) influence the homeostasis of bone. 4

Osteoclasts

Osteoid

Osteoblasts

New osteon

OPG

Osteoblast/stromal precursor cell

RANKL

RANK receptor

Osteoclast precursor cell

Activated osteoclast

Bone

Differentiation