The matrix also contains other matrix (noncollagenous) proteins that constitute the ground substance of bone. As a minor component of bone, constituting only 10% of the total weight of bone matrix proteins, they are essential to bone development, growth, remodeling, and repair. Both the collagen and the ground substance become mineralized to form bone tissue. The four main groups of noncollagenous proteins found in the bone matrix are the following:  Proteoglycan macromolecules contain a core protein with various numbers of covalently attached side chains of glycosaminoglycans (hyaluronan, chondroitin sulfate, and keratan sulfate). They contribute to the compressive strength of bone. They are also responsible for binding growth factors and may inhibit mineralization. Proteoglycans are described in detail in Chapter 6 (Table 6.3, page 176).
 Multiadhesive glycoproteins are responsible for attachment of bone cells and collagen fibers to the mineralized ground substance. Some of the more important glycoproteins are osteonectin (which serves as a glue between the collagen and hydroxyapatite crystals) and sialoproteins such as osteopontin (which mediates attachment of cells to bone matrix) and sialoprotein I and II (which mediate cell attachment and initiate calcium phosphate formation during the mineralization process).
 Bone-specific, vitamin K–dependent proteins, which include osteocalcin (which captures calcium from the circulation and attracts and stimulates osteoclasts in bone remodeling), protein S (which assists in the removal of cells undergoing apoptosis), and matrix Gla-protein (MGP) (which participates in the development of vascular calcifications).
 Growth factors and cytokines, which are small regulatory proteins including insulinlike growth factors (IGFs), tumor necrosis factor (TNF-), transforming growth factor (TGF-), platelet-derived growth factors (PDGFs), bone morphogenic proteins (BMPs), and interleukins (IL-1, IL-6). The most unique members of this group are BMPs, because they induce the differentiation of mesenchymal cells into osteoblasts, the bone-producing cells. Recombinant human BMP-7, also known as osteogenic protein-1 (OP-1), is now used clinically to induce bone growth after bone surgery involving large bone defects, spinal fusions, or implantation of graft materials.
Bone matrix contains lacunae connected by a network of canaliculi.
Within the bone matrix are spaces called lacunae (sing., lacuna), each of which contains a bone cell, or osteocyte.
The osteocyte extends numerous processes into small tunnels called canaliculi. Canaliculi course through the mineralized matrix, connecting adjacent lacunae and allowing contact be tween the cell processes of neighboring osteocytes (Plate 11, page 244). In this manner, a continuous network of canaliculi and lacunae-containing cells and their processes is formed throughout the entire mass of mineralized tissue. Electron gap junctions. Bone tissue depends on the osteocytes to maintain viability. In addition to osteocytes, four other cell types are associ ated with bone.
 Osteoprogenitor cells are cells derived from mesenchymal stem cells; they give rise to osteoblasts.
 Osteoblasts are cells that secrete the extracellular matrix of bone; once the cell is surrounded with its secreted matrix, it is referred to as an osteocyte.
 Bone-lining cells are cells that remain on the bone surface when there is no active growth. They are derived from those osteoblasts that remain after bone deposition ceases.
 Osteoclasts are bone-resorbing cells present on bone surfaces where bone is being removed or remodeled (reorganized) or where bone has been damaged.