Issue link: https://wardsworld.wardsci.com/i/1510309
3 Bone (continued) + ward ' s science organic matrix of bone and provides the tensile strength neces- sary to resist bending and stretching forces. Collagen fibers are embedded in the mineralized matrix of bone, contributing to its overall structural integrity. Osteonectin [also known as secreted protein, acidic and rich in cysteine (SPARC)] is a glyco- protein that helps regulating the deposition and mineralization of calcium and other minerals in bone tissue and plays a role in bone remodeling and repair. Osteopontin plays a role in cell adhesion and is involved in various cellular processes within bone tissue, including bone remodeling, mineralization, inflam- mation, and the repair of bone fractures. Bone sialoprotein is a glycoprotein important for nucleating and regulating the depo- sition of calcium phosphate crystals during the mineralization of bone. It also interacts with cell surface receptors, contribut- ing to cell-matrix interactions in bone tissue. Both biglycan and decorin are proteoglycans involved in regulating the organiza- tion and assembly of collagen fibers within bone tissue. These proteoglycans help maintain the structural integrity of the ex- tracellular matrix. Osteocalcin (also known as bone Gla protein) is produced by osteoblasts and contributes to mineralization by binding to calcium ions and helping to incorporate them into the bone matrix. Osteocalcin also participates in the regulation of bone turnover and may have hormonal functions, influenc- ing glucose metabolism and other physiological processes. Bone cells Bone is rich in blood vessels and nerves, and thus contains the cell types associated with these structures. However, the prima- ry cell types in bone are those that result in its formation and maintenance (osteoblasts and osteocytes) and those that are responsible for its removal (osteoclasts). Osteoblasts form from the differentiation of multipotential stromal cells that reside in the periosteum and the bone marrow. Under the appropriate stimuli, these primitive stromal cells mature to bone-forming cells at targeted sites in the skeleton. Under different stimuli, stromal cells are also capable of developing into adipocytes (fat cells), muscle cells, and chondrocytes (cartilage cells). Osteo- cytes, which are osteoblasts that become incorporated within the bone tissue itself, are the most numerous cell type in bone. They reside in spaces (lacunae) within the mineralized bone, forming numerous extensions through tiny channels (canalicu- li) in the bone that connect with other osteocytes and with the cells on the endosteal surface (Fig. 4). Osteocytes are therefore ideally placed to sense stresses and loads placed on the bone and to convey this information to the osteoblasts on the bone surface, thereby enabling bone to adapt to altered mechani- cal loading by the formation of new bone. Osteocytes play a crucial role in detecting and directing the repair of microscopic damage that frequently occurs in the bone matrix due to wear and tear of the skeleton. Failure to repair the cracks and micro- fractures that occur in bone, or when this microdamage accu- mulates at a rate exceeding its repair, can cause the structural failure of the bone. This is seen, for example, in athletes where repeated loading of the bone leads to stress fractures. Numerous molecules that regulate the formation and func- tion of osteoblastic cells have been identified. The products of particular homeobox genes, which determine the tissue type that the primitive cells will become, are especially important in the embryological development of the skeleton. Subsequently, circulating hormones, such as insulin, growth hormone, and insulinlike growth factors, combine with growth factors within the bone itself, such as transforming growth factor beta (TGFβ) and bone morphogenetic proteins (BMPs), to influence the differentiation of osteoblasts for the growth and repair of bone. During bone growth and in fracture repair, the sequential response of osteoblasts and their precursors to these influences controls each step in the cell differentiation pathway, as well as the secretory activity of the mature osteoblasts. Osteoclasts are typically large, multinucleated cells, and they are rich in the intracellular machinery required for bone resorption. This is accomplished when the cells form a tight sealing zone by attachment of the cell membrane against the bone matrix, creating a bone-resorbing compartment. Into this space, the cell secretes acid to dissolve the bone mineral, and enzymes to digest the collagen and other proteins in the bone matrix. The removal of bone by osteoclasts is necessary to enable the repair of microscopic damage and changes in bone shape during growth and tooth eruption. Osteoclast- mediated bone resorption is also the mechanism for releasing calcium stored in bone for the maintenance of calcium levels in the blood. The level of calcium in the blood is monitored by the parathyroid gland and by the cells of the thyroid. If the level drops too low, parathyroid hormone is released to prevent the loss of calcium through the kidneys and to mobilize calcium from bone. If the blood calcium level is too high, the hormone Fig. 4: Osteons in the the context of compact bone. (Copyright © McGraw Hill)