(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.
Bone: Current Research on Isolation or Production of Therapeutic Cells
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Bone: Current Research on Isolation or Production of Therapeutic Cells
Bone is one of the tissue types that undergo constant remodeling during the lifetime of the organism. By virtue of this property, bone is mostly able to regenerate. Healing of fractures is one example of bone regenerating, but regeneration potential is limited, and some autoimmune diseases are associated with erosion of the bone. Traumatic injuries also result in non-union fractures—fractures that do not heal, as there is no union. A fix for such situations is to create a micro-environment in which bone regeneration is more efficient. Bone morphogenic protein or BMP is one of the factors that promote efficient regeneration of the bone. This requires topical application to the site of injury, which then promotes efficient regeneration. Disadvantages of this method include that it does not prevent the invasion of soft tissue and that it promotes random regeneration of tissue surrounding the wound site. In other cases, application of BMP alone is insufficient to promote fracture or bone healing. A bone graft is necessary if the stem cells and other bone cells are present. The bone graft provides an environment of growing bone cells, and these bone grafts help regenerate the tissue to facilitate regeneration. The bone is grafted from other parts of patients’ own bodies. When bone of that nature is unavailable, doctors resort to isolating the graft from cadavers. Issues of immunogenicity or bone rejection are in play when the grafts are isolated from sources other than the patient’s body.
Bone Grafting
Bone grafting is a surgical procedure in which the bone from a healthy site is removed surgically. The bone is then carved in the shape of the wound and prepared to close the wound. This graft is then placed at the wound site and held in place with pins and plates. The bone graft provides a niche of healthy cells growing and regenerating. When the bone graft is accepted by the body, the cells regenerate to close the wound leading to union of fractures.
However, healthy individuals might not have graftable bone, and it is difficult to find a match in cadavers. This significant technical difficulty was overcome with the discovery of stem cells. Stem cells that are pluripotent can differentiate into bone stem cells when treated with appropriate hormones and these cells are differentiated on substrates, such as ceramics and polymers. These ceramics are not immunogenic and are easily integrated in the body but also provide a medium and structure for the bone cells to differentiate and grow outside the body. A synthetic bone graft is then placed in the wound. The stem cells provide a population of growing and differentiating cells that regenerate the bone. In this section, the process of stem cell isolation from the patient body and stem cells propagation in vitro for therapeutic purposes will be explained. Significant