Bone remodeling osteoclasts

Bone tissue is constantly being renewed by the concerted action of osteoblasts and osteoclasts. Bone remodeling has two main phases a resorption phase consisting in the removal of old bone by osteoclasts, and a later phase of new bone formation driven by osteoblasts [6], Thus, the activity of osteoblasts and osteoclasts determines bone mass, bone geometry, bone quality, and, subsequently, bone strength [7, 8]. Osteoporosis is a prevalent disorder consisting in decreased bone mass and/or abnormal bone microarchitecture that impairs bone strength and increases the risk of fracture. Therefore, patients with osteoporosis may suffer fractures as a result of minor trauma, or even in the absence of trauma. The most common osteoporotic fractures are those of the vertebral bodies, the hip, the wrist, the shoulder, and the pelvis. 

Bone remodelling, which continues throughout adult life, is necessary for the maintenance of normal bone structure and requires that bone formation and resorption should be balanced. Bone remodelling occurs in focal or discrete packets know as bone multicellular unit (BMU). In this process, both bone formation and resorption occur at the same place so that there is no change in the shape of the bone. After a certain amount of bone is removed as a result of osteoclastic resorption and the osteoclasts have moved away from the site, a reversal phase takes place in which a cement line is laid down. Osteoblasts then synthesize matrix, which becomes mineralised. The BMU remodeling sequence normally takes about 3 months to produce a bone structure unit (Fig. 2). 

Bone Resorption The removal of mineralised bone by osteoclasts. Bone resorption, which is part of the bone remodelling process, includes the release of mineral (mostly calcium and phosphate) and subsequent proteolysis of organic matter (mostly collagen). 

Under normal circumstances, the skeleton undergoes a dynamic process of bone remodeling. Bone tissue responds to stress and injury through continuous replacement and repair. This process is completed by the basic multicellular unit, which includes both osteoblasts and osteoclasts. Osteoclasts are involved with resorption or breakdown of bone and continuously create microscopic cavities in bone tissue. Osteoblasts are involved in bone formation and continuously mineralize new bone in the cavities created by osteoclasts. Until peak bone mass is achieved between the ages of 25 and 35, bone formation exceeds bone resorption for an overall increase in bone mass. Trabecular bone is more susceptible to bone remodeling in part owing to its larger surface area. 

An in vitro cell model resembles the remodeling process of osteoclastic bone resorption followed by osteoblastic bone formation investigate the influence of lead on the communication between these cells determine if lead in the medium (i.e. extracellular fluid) or in the matrix (i.e. in the bone) has different effects on osteoclasts and osteoblasts... 

The adult skeleton is periodically remodeled by transitory anatomic structures that contain juxtaposed osteoclast and osteoblast teams and that replace old bone with new bone. The purpose of this remodeling is both to prevent bone aging and repair the damage that occurs as well as to guarantee a contribution of minerals, especially calcium, to body cells for their correct function. In the last few years, due mainly to the research in molecular biology and cellular differentiation and to studies of genetically manipulated mice, it has been possible to discover many aspects both of the cellular and molecular bases of this bone remodeling as well as of the differentiation and function of the two main implied cell types osteoblasts and osteoclasts. 

The most important cells implied in bone remodeling are the osteoclasts and osteoblast, although in this process different cellular types such as endothelial... 

For bone substitutes, it is very important that bioceramics have a considerable degree of porosity and particularly interconnected pores so that living bone grows rapidly into the pores. Special bone remodeling cells called osteoclasts and osteoblasts play an extremely important part of the process of rebuilding or repairing the bone. 

Osteoblasts (top) deposit collagen, as well as Ca "" and phosphate, and thereby create new bone matter, while osteoclasts (bottom) secrete H"" ions and collagenases that locally dissolve bone (bone remodeling). Osteoblasts and osteoclasts mutually activate each other by releasing cytokines (see p. 392) and growth factors. This helps keep bone formation and bone breakdown in balance. 

Osteopetrosis is another rare disease in humans that has been analyzed by IR imaging. Patients with this disease have bones that are like rock, impeding their mobility and increasing their pain. In many patients, the cause of the disease is the inability of the bone resorbing cells, osteoclasts, to remodel the bone. For this reason there is a persistence of calcified cartilage. The IR data demonstrated increased mineral content and decreased crystal size, consistent with the properties seen in the bones of animal models of this disease.13... 

Figure 1. The cellular activity during bone remodelling. At the tip (cutting cone) multi-nucleated osteoclasts (OCLs) excavate the mineralised bone tissue. At some distance, after the resting zone, osteoblasts (OBLs) refill the tunnel with (osteoid) that is subsequently mineralised. Osteocytes (OCYs) are former osteoblasts that were entombed within the bone matrix, but remained connected to the bone surface by numerous long slender protrusions (not visible). Courtesy R. Schenk.

Both cortical and trabecular bone are continuously remodeled through the formation of a bone-modeling unit (BMU), or cutter-cone this process involves activation of osteoclasts, leading to resorption of bone by osteoclasts and formation of new bone by osteoblasts on the site of the old, resorbed bone (Fig. 7) (Martin and Burr, 1989). Under normal physiological conditions (i.e., in the absence of either growth or disease) the dynamics of bone remodeling maintain bone homeostasis throughout a person s lifetime. 

Interleukin-6 (IL-6) is a principal cellular regulatory factor, and also plays a role in bone remodeling. IL-6 exercises its effect by binding to a receptor (IL-6R), which leads to signal transduction and activation of intracellular cascades. Information from studies performed both in vitro and in vivo show IL-6 as an autocrine/paracrine factor of the osteoclasts. Recent studies describe especially increased expression of IL-6R mRNA in the osteoclasts engaged in increased bone resorption. It can be judged that IL-6 itself is in a sophisticated way involved in bone resorption, and that especially the expression of its receptor (IL-6R) correlates with resorption activity of the osteoclasts (LI). 

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