The osteoblast, or bone-forming cell, is approximately 20 µm in diameter and contains a single eccentric nucleus. Under the direction of RUNX2 and Osterix transcription factors, osteoblasts arise from osteoprogenitor cells found in the apical cell layers of periosteum and within marrow tissue. Osteoblasts adhere to an organic matrix scaffolding called osteoid (found on periosteal, endosteal, trabecular, and haversian surfaces). Osteoblasts also preside over the mineralization of osteoid, leading to the formation of new bone tissue. The osteoblast phenotype is identified by its large quantities of bone alkaline phosphatase and its production of a bone-specific matrix protein called osteocalcin.

The mature osteocyte, derived from an osteoblast, is an oval cell 20 to 60 µm long and buried within the mineralized bone matrix in a small cavern called a lacuna. Numerous processes extend from its cell surface and leave the lacuna via a network of canals or canaliculi. Many osteocyte processes extend into the canalicular system and contact processes from other osteocytes. This extensive osteocyte-canaliculi network is believed to play a vital role in transportation of cell metabolites, communication between cells, and regulation of mineral homeostasis.

The other major type of bone cell, the osteoclast, resorbs mineralized bone matrix. The osteoclast is a large cell (as great as 100 µm in diameter) containing as many as 100 nuclei per cell (although most osteoclasts contain many fewer nuclei). It is rich in lysosomal enzymes (including acid phosphatase and proteases) and proton pumps and possesses a specialized cell membrane (the ruffled border) at sites where active bone resorption occurs. Unlike the osteoblast and the osteocyte that derive from a mesenchymal progenitor cell, the osteoclast is derived from circulating cells of the monocyte-macrophage lineage that differentiate into preosteoclasts near a bone’s surface.

Bone cells account for only a small portion (2%) of the entire organic component of bone, most of which consists of osteoid produced by osteoblasts.

Collagen (predominantly type I) is the major organic component of bone, accounting for a majority of the protein in osteoid. Bone collagen is deposited along lines of mechanical stress according to Wolff’s law and provides an important template for mineral crystal deposition (see Plate 2-36). Although constituting only a minor portion of osteoid’s protein content, noncollagenous bone proteins play important roles in regulating osteoblast proliferation, metabolism, matrix production, and mineralization of bone matrix. Major noncollagenous proteins found in bone include fetuin (α₂-HS-glycoprotein), osteonectin, osteopontin, osteocalcin (bone Gla protein), bone sialoprotein, decorin and biglycan proteoglycans, bone proteolipid, and bone morphogenic proteins.