Advances in osteoclast biology resulting from the study of osteopetrotic mutations

Abstract

Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast phenotypes, we discuss how osteopetrosis models have clarified the function of the coupling of bone formation to bone resorption, and the pivotal role of the osteoclast and their function in this phenomenon. We highlight the distinct possibility that osteoclast activities can be divided into two separate avenues: bone resorption and control of bone formation.

An Investigative Study Into the Relationship of Bone Morphogenetic Protein Antagonist Expression and Osteocyte Density by Region and Quadrant

“…Second, it provides protection for major organ systems, such as the cardiac and respiratory systems, as well as providing a home and protection for marrow. Finally, it is a storage center for many ions and minerals required for metabolic function, including calcium, phosphorus and a multitude of growth factors (Segovia-Silvestre, et al, 2009). Many early studies concerning bone focused on the role of bone as a mineral reservoir (Martin, et al, 1998).…”

“…Mature osteoblasts are rarely if ever found alone however; they seem to exist in small clusters consisting of a mix of active bone-forming osteoblasts and their bone lining cell cousins (Segovia-Silvestre, et al, 2009). Bone formation begins as osteoblasts secrete type 1 collagen onto existing bone surfaces.…”

“…This newly formed matrix is composed of unmineralized bone matrix, referred to as osteoid, and is laid down at a rate of about 1 micron a day (Martin, et al, 1998;Segovia-Silvestre, et al, 2009). Once the osteoid is formed, osteoblasts begin to mineralize this newly formed bone along the mineralization or calcification front by secreting vesicles which contain concentrations of calcium and phosphate in high enough levels to allow crystal formation, while also removing some of the water content (Manolagas, 2000).…”

“…Secretion of additional molecules required for correction matrix mineralization is also performed by this cell type. These include: osteocalcin, osteopontin, osteonection, and bone sialoprotein (Segovia-Silvestre, et al, 2009). …”

“…These large cells are responsible for resorbing old or unused bone, releasing minerals that can be transported throughout the body (Roodman, 1999). Resorption begins along the brush or ruffled borders of the osteoclasts as protons are secreted by a specific ATPase in conjunction with passive transport of chloride ions (Figure 3) (Martin, et al, 1998;Segovia-Silvestre, et al, 2009). Catalyzation of carbon dioxide and water into H 2 CO 3 , followed by catalyzation into H+ and HCO 3 , generates these ions within the cells (Segovia-Silvestre, et al, 2009).…”