The Architecture and Cellular Elements of Bone

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The Organization of Skeletal Tissues

The major compartments of bone include: 1) the periosteum or outer fibrous envelope of cortical bone.  The periosteum contains highly specialized cells which  are osteogenic and which contain genes for locally acting growth factors.  2) The bone cortex, the outer bony layer which contains Haversian canals, the sites of cortical bone remodeling, and 3) the inner compartment or marrow space which contains both osteogenic and blood-forming cells.  The cellular elements are contained within an interconnecting system of plate-like bone also termed  lamellar or trabecular  bone.

Skeletal tissues develop via two distinct processes: intramembranous and endochondral bone formation.  Intramembranous bone formation involves the growth of mesenchymal cells in a highly vascularized area of embryonic primordium that differentiate into bone forming cells, pre-osteoblasts and osteoblasts. Embryonic bone, containing irregularly oriented collagen fibrils termed woven bone, is initially formed.   Following remodeling, woven bone is replaced by mature trabecular (lamellar) bone.  Examples of intramembranous bone include the calvarium, scapula and ilium.

Endochondral bone formation  occurs when  mesenchymal cells within the embryonic anlage undergo differentiation into prechondroblasts and mature chondroblasts.  These cells secrete a cartilagenous matrix that forms the template in which matrix calcification occurs. Calcification of the matrix in both the periosteal layer and at the growth plate (epiphysis) follows hypertrophy and apoptosis of chondrocytes with the appearance of osteoblastic stromal cells derived from intramembranous bone formation that occurs in perichondeal (periosteal) zone of apposition. Vascular ingrowth into this periosteal zone of woven bone faciltates the development of hematogenous marrow and the movement of osteoprogenitor cells into the marrow space. Endochondral bone formation at the growth plate follows cartilage deposition, hypertrophy of chondrocytes, vascularization, the removal of the cartilagenous matrix by osteoclasts and the subsequent replacement of cartilaginous lamellae by mature bone formed by differentiated osteoblasts. 

Cellular Elements Determining Bone Remodeling

Bone mass changes constantly throughout our lifetimes, albeit more slowly than is typical for other organs, and in a manner that is non-uniform from site to site. The metabolic rate or remodeling rate in lamellar bone is 6 times more rapid than that in cortical bone. Thus, in situations where bone loss is stimulated, rapid loss will occur first in areas rich in trabecular bone such as the vertebral bodies, and later in  cortical bone sites. Although this is evident as we watch children develop from infancy through adolescence to adulthood, we tend to underestimate the dynamic state of skeletal tissue in older individuals

The cellular elements in bone responsible for bone formation and resorption have been recognized to form a functional unit termed the basic multicellular unit (BMU, Frost 1969).

Osteoprogenitor Cells: Also termed bone marrow stromal cells, osteoprogenitor cells which are initially fibroblastic in appearance, differentiate into preosteoblastic and mature osteoblastic cells lining the endosteal surfaces of bone.

The term osteoprogenitor or marrow stromal cell is restricted to multipotential cells of the adherant stromal fibroblastic system of bone marrow.  By definition these include osteoblasts and pre-osteoblasts found near the bone surfaces, fibroblasts and reticular cells, terms commonly used for the soft tissue connective tissue cells of marrow, and  blood vessel walls and marrow adipocytes. The proposed lines of stromal cells have been designated fibroblastic, reticular, adipocytic and osteogenic.

Recent studies have focused on the role played by stromal cells in the maintenance of the osteoblast pool and its replenishment during normal bone remodeling and following fracture.  Initially described by Friedenstein et al., the function of osteoprogenitor cells has been studied under a variety of conditions including normal aging where cell activity declines, following stimulation with hormones and growth inducing peptides, and in the rat hindlimb  suspension model of microgravity. 

Osteoblasts: The osteoblast is the differentiated product of the marrow stromal cell that directs the deposition of bone matrix and its calcifiation.

Osteoclasts: The osteoclast is the major bone resorbing cell.  Osteoclasts differentiate from early bone marrow precursors of the granulocyte macrophage family that differentiate into mononuclear precursor cells (pre-ostoclasts) and that form mature osteoclasts under the influence of several differentiating factors including interleukin-1, tumor necrosis factor, (TNF),  PTH and 1,25 (OH)2 Vit D.  The mature osteoclast is a multinucleated cell with a characteristic ruffled border that overlies the endosteal surface forming a bone resorbing compartment.  The attachment is dependent on specific cell-surface integrin receptors that bind to specific matrix protein sequences.  The osteoclast synthesizes lysosomal enzymes including tartrate-resistant acid phosphatase (TRAP), and collagenases that are secreted via the ruffled border into this extracellular space. Osteoclasts synthesize carbonic anhydrase and H+  exchangers (Na K ATPase, HCO3/Cl and NA/H exchangers) that facilitate the secretion of acid across the ruffled border into the sealed zone thus inducing resorption of the underlying bone matrix.

Osteocytes: The osteocyte is the final differentiation stage for the osteoblast. During the process of bone formation, osteoblasts on the endosteal surface are incorporated into bone matrix where they form osteocytes.  Mature osteocytes are stellate-shaped cells enclosed in the lacunar-canalicular system of mineralized bone matrix.  The dendritic processes of individuals osteocytes are in contact with other cells though the canalicular system thus providing a syncitial meshwork of cells that communicate with each other through cell membrane gap junctions.  Osteocytes, are extremely sensitive to mechanical stress, a quality that is probably linked to the process of mechanical adaptation (Wolff's law). The in vivo operating cell stress derived from bone loading is likely a flow of an interstitial fluid along the surface of the osteocytes and lining cells.

Lining Cells: These are flattened cells which line trabecular surfaces.  Lining cells are one stage in the formation of the osteocyte which is embedded in cortical bone matrix.   Although not well characterized, it is likely that the lining cells elaborate a number of  growth factors and cytokines.