to grow at the site, become mineralized, and form bone. Alkaline phosphatase is present on the osteoblast surface until they either differentiate into osteocytes or bone lining cells. Bone lining cells are inactive osteoblasts that line the surface of all the bony spicules of spongy bone. Once activated, they become osteoblasts and deposit new bone. Their retraction and exposure of the surface of the bone matrix initiates resorption of bone in the dynamic process of bone remodeling.
Osteoblasts communicate using their cytoplasmic processes in a cellular organization called a syncytium. As osteoblasts are continually secreting osteoid around them, they often become surrounded by their own secretion, at which point they are known as osteocytes. Alternatively, osteoblasts can cover the surface of the bone as bone lining cells. Bone lining cells are essentially inactivated osteoblasts and can be reactivated to continue their secretory function. They also play a role in osteoclast recruitment as they cover and uncover the surface of the bone.
Osteoclasts
Osteoclasts are large cells that perform a complementary function to osteoblasts. Derived from a fusion of multiple precursor monocytes (uninucleated cells that can differentiate into various phagocytic cells), osteoclasts are multinucleated and phagocytotic (they possess the ability to ingest and degrade extracellular substances).
Each osteocyte has two surfaces: a smooth surface facing away from the bone and a highly evaginated/ruffled or active surface adjacent to the bone surface that increases the surface area for the secretion of hydrolytic enzymes for digestion of amorphous/inorganic/mineralized bone, leaving exposed the organic collagen fibers. Due to the many secretory granules, osteoclasts must maintain many vesicles (a cell storage organelle), which they secrete through their ruffled border.
When activated, an osteoclast has the ability to secrete hydrolytic enzymes and acid, which can degrade the mineralized organic matrix deposited by osteoblasts. The resorbed portion of the surface of the bone is termed a Howship’s lacunae and is separated from space outside the bone by attachments of the osteoclast’s plasma membrane to the peripheral bone. This belt-like seal between the two surfaces is termed the sealing zone, which compartmentalizes the working area of the osteoclast so that the digestive processes can be controlled. The sealing zone has actin filaments that attach to osteopontin in the mineralized bone surface through integrins.
Osteoclast activation and action are regulated by two main hormones: parathyroid hormone (PTH) and calcitonin. PTH is released in response to low calcium levels and thus upregulates osteoclast activity as it releases more calcium from bone. Calcitonin is released in response to high calcium levels and has the opposite effect on overall osteoclast activity.
Osteocytes
Osteocytes arise as the result of osteoblasts surrounding themselves in their own mineralized osteoid. Smaller than osteoblasts, osteocytes arrange themselves in a circular formation around the Haversian canal in a morphological unit called an osteon. Each osteocyte resides in a space in the bone called a lacuna, and their cytoplasmic extensions are termed canaliculi. These cytoplasmic extensions connect the osteocytes to one another and to the blood source in concentric rings through the bone. Osteocyte processes exhibit gap junctions that facilitate cell-to-cell communication. A very small space between cell and bone is filled with bone fluid that allows nutrients to diffuse through the ossified mass.
Although osteocytes are relatively inactive, they are dynamic components of bone tissue and have been demonstrated to be able to synthesize molecules and transmit signals. Osteocytes participate in osteocytic osteolysis, or the resorption of perilacunar bone, resulting in enlargement of the lacunae. They also form new bone matrix and control mineralization. Osteolysis from osteocytes is thought to be responsible for rapid adjustments in calcium levels in the serum responding to calcium and phosphate levels in the extracellular fluid.
Bone Marrow
There are two main types of bone marrow: red and yellow. These two marrows are quite similar except that yellow marrow has more adipocytes or fat cells. Bone marrow has several other types of cells, including fibroblasts, mesenchymal stem cells, osteoblasts, osteoclasts, erythroid progenitor cells (red blood cell precursor), and myelopoietic precursor cells (the precursor to various immune cells).
Myelopoietic precursor cells. Myelopoietic precursor cells give rise to three distinct cell types: basophils, neutrophils, and eosinophils. Starting with a nucleus that spans much of the cell and is of a relatively light color, myelopoietic precursor cells eventually become smaller, with fragmented nuclei and visible secretory granules. In the line of descent that leads to neutrophils, the stem cells become what are called band cells and their nuclei resemble horseshoes. The main visible difference between basophils, neutrophils, and eosinophils when stained with haematoxylin and eosin is that basophils appear dark blue, neutrophils appear light purple, and eosinophils appear tinged orange. All of these cells are pivotal in immunity as they are leukocytes, or white blood cells. Eosinophils are noted for their ability to fight viral infection, basophils for their role in inflammation, and neutrophils (by far the most common leukocyte) for their antimicrobial function.
Erythroid precursor cells. Starting off as large proerythroblasts, erythroid precursors go through various intermediates before becoming erythrocytes, or red blood cells. As proerythroblasts, the cells have large nuclei with visible nucleoli and chromatin that resembles lace. Moving through the various stages of development, the cells and nuclei get smaller and denser. At the stage of the polychromatic erythroblast, the cells lose their ability to divide. Afterwards, the cells become even smaller and the nucleus is pyknotic in appearance, during which the nucleus is ready to be extruded and the cells become termed orthochromatic erythroblasts. Once the cells have extruded the nucleus they are termed reticulocytes and are quite similar to erythrocytes. The lack of a nucleus is necessary in erythrocytes in order to maximize oxygen-carrying capacity and transport, which is mediated by hemoglobin, a protein that binds oxygen with high affinity.
Mesenchymal stem cells. Mesenchymal stem cells play an important role in bone as they have the ability to differentiate into osteoblasts, chondrocytes, and adipocytes. Bone marrow differentiation into chondrocytes is uncommon due to the high degree of vascularity and the negative effect it has on cartilage formation (as chondrocytes deposit cartilage as opposed to osteoblasts, which deposit bone).
Fibroblasts. Fibroblasts mainly synthesize the bone marrow’s extracellular matrix and secrete collagen. However, they have also been shown to have a role in the regulation of hematopoiesis through direct cell-to-cell contact.
Krishna S. Vyas
University of Kentucky College of Medicine
Madhav Bole
University of Western Ontario
See Also: Bone: Development and Regeneration Potential; Bone: Major Pathologies.
Further Readings
Bianco, Paolo, et al. “Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications.” Stem Cells, v.19/3 (2001).
Dorshkind, Kenneth. “Regulation of Hemopoiesis by Bone Marrow Stromal Cells and Their Products.” Annual Review of Immunology, v.8/1 (1990).
Pritchard, J. J. “General Histology of Bone.” In G. H. Bourne, The Biochemistry and Physiology of Bone (2nd ed., vol. 1). New York: Academic Press, 1972.
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