Osteoclasts in bone metabolism
Hakeda, Y.; Kumegawa, M.
Kaibogaku Zasshi. Journal of Anatomy 66(4): 215-225
1991
ISSN/ISBN: 0022-7722 PMID: 1759556 Document Number: 373559
Bone resorption plays an important role in bone modeling and remodeling. Osteoclasts are the cells responsible for the bone resorption. Osteoclasts are located on endosteal bone surfaces and on the periosteal surface beneath the periosteum. They are multinucleated giant cells highly polarized in their morphology and function. Among the proximal surface, the membrane and the area of the cytoplasm directly oppose to the bone surface, which are specialized into two regions. A central region consisting of many irregular cytoplasmic processes and infoldings, the ruffled border, is known to be the active site of bone resorption. Surrounding the ruffled border, a second region, the clear zone provides an area of close attachment to the mineralized bone surface. The osteoclasts secrete a large amount of protons by the action of H+-pump on the ruffled border into the sealed resorption cavity, resulting in the acidified microenvironment under which condition of the bone matrix is dissolved. Protons are provided by the intracellular action of carbonic anhydrase. Following the secretion of the protons, several ion-transporting systems, i.e., carbonate-chloride exchanger, chloride-channel, Ca2+-transport systems. Na+/K+- ATPase, and voltage-dependent Ca2+ channel, are sequentially operated on both apical and basolateral cytoplasmic membranes. In addition, osteoclasts contain a large amount of lysosomal enzymes (cathespsin C, beta-glycerophosphatase, beta-glucuronidase, etc.), which contribute to degrade the bone organic matrices exposed in the resorption cavity. These enzymes bind to the mannose-6-phosphate receptor on Golgi apparatus, are transported to the ruffled border and are secreted into the extracellular compartment in an exocytotoxic manner. Osteoclasts also have a high tartrate-resistant acid phosphatase activity which is currently used as a marker enzyme osteoclastic differentiation. Osteoclasts are considered to develop from hematopoietic stem cells. So far, the following four different pathways of the differentiation of osteoclast are proposed: the precursors of osteoclast develop (1) from multilineage hematopoietic cells via a completely separate differentiation line, (2) from granulocyte macrophage-colony forming cells, (3) from committed but proliferative monocyte-macrophage, and (4) from mature and unproliferative monocyte-macrophage. However, the differentiation line of the osteoclasts has still to be elucidated. The formation of osteoclasts as well as that of other hematopoietic cells is strongly regulated by many cytokines [interleukin (IL)-1, IL-3, IL-6, M-colony stimulating factor (CSF), and GM-CSF]. 1,25-Dihydroxyvitamin D3 and parathyroid hormone also stimulate the differentiation of osteoclast precursors. However, the mature osteoclasts do not possess the receptors for these hormones. This means that as differentiation proceeds, the receptors for PTH and 1,25 (OH2D3 disappear on the osteoclasts. Thus, such a change in the number of receptor sites of osteotropic factors plays an important role in regulation of osteoclastic differentiation. The osteoclasts, of course, are present only in bone tissue. In view of this, stromal cells in bone tissue, including osteoblasts, are thought to have an important and physiological role in regulating osteoclastic formation and function. At present, a lot of evidence has been reported that osteoblastic and preadipocytic cells strongly and significantly modify the differentiation and activation by a cell-cell contact and/or humoral factors secreted by them. The elucidation of these interactions is one of the major subjects in the bone field.