Browsing by Subject "Osteolysis"

Now showing 1 - 3 of 3
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    Arteria1 microvascularization and breast cancer colonization in bone
    (Murcia : F. Hernández, 1997) Yoneda, T.
    Bone is one of the most preferential target organs of cancer metastases. Breast, prostate and lung cancers have a special predilection for colonization in bone. In an animal model in which inoculation of cancer cells into the left cardiac ventricle selectively develops osteolytic bone metastases but rarely forms metastases in non-bone organs, the pattern of breast cancer colonization in bone was studied radiologically and histologically. Colonization of cancer cells in bone was found to initiate and develop along with or at the terminal end of the major arteries running into bone. It should, therefore, be re-recognized that the anatomical vasculature still remains as a critica1 factor which influences cancer colonization in bone in addition to cellular and molecular properties of the bone microenvironment and metastatic cancer cells.
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    Canonical and non-canonical pathways of osteoclast formation
    (Murcia : F. Hernández, 2009) Knowles, H.J.; Athanasou, N.A.
    Physiological and pathological bone resorption is mediated by osteoclasts, multinucleated cells which are formed by the fusion of monocyte / macrophage precursors. The canonical pathway of osteoclast formation requires the presence of the receptor activator for NFkB ligand (RANKL) and macrophage colony stimulating factor (M-CSF). Noncanonical pathways of osteoclast formation have been described in which cytokines / growth factors can substitute for RANKL or M-CSF to induce osteoclast formation. Substitutes for RANKL include LIGHT, TNFa and interleukins 6, 11 and 8. M-CSF substitutes include vascular endothelial growth factor (VEGF), placental growth factor (PlGF), FLt-3 ligand and hepatocyte growth factor (HGF). These growth factors can also influence canonical (RANKL / M-CSFinduced) osteoclast formation. Both canonical and noncanonical pathways of osteoclast formation play a role in the formation of osteolytic lesions where there is increased osteoclast formation and activity, such as in giant cell tumour of bone.
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    Structure and function of V-ATPases in osteoclasts: potential therapeutic targets for the treatment of osteolysis
    (Murcia : F. Hernández, 2007) Xu, J.; Cheng, T.; Feng, H.T.; Pavlos, N.J.; Zheng, M.H.
    Excessive activity of osteoclasts becomes manifest in many common lytic bone disorders such as osteoporosis, Paget’s disease, bone aseptic loosening and tumor-induced bone destruction. Vacuolar proton pump H+-adenosine triphosphatases (V-ATPases), located on the bone-apposed plasma membrane of the osteoclast, are imperative for the function of osteoclasts, and thus are a potential molecular target for the development of novel anti-resorptive agents. To date, the V-ATPases core structure has been well modeled and consists of two distinct functional domains, the V1 (A, B1, B2, C1, C2, D, E1, E2, F, G1, G2, G3, and H subunits) and V0 (a1, a2, a3, a4, d1, d2, c, c’ e1, e2 subunits) as well as the accessory subunits ac45 and M8-9. However, the exact configuration of osteoclast specific V-ATPases remains to be established. Inactivation of subunit a3 leads to osteopetrosis in both mice and man because of nonfunctional osteoclasts that are capable of acidifying the extracellular resorption lacuna. On the other hand, inactivation of subunits c, d1 and ac45 results in early embryonic lethality, indicating that certain subunits, such as a3, are more specific to osteoclast function than others. In osteoclasts, V-ATPases also cooperate with chloride channel protein CLC-7 to acidify the resorption lacuna. In addition, development of V-ATPases inhibitors such as bafilomycin A1, SB 242784 and FR167356 that selectively target osteoclast specific VATPases remains a challenge. Understanding the subunits of V-ATPase regulate osteoclast function might facilitate the development of novel and selective inhibitors for the treatment of lytic bone disorders. This review summarizes recent research developments in VATPases with particular emphasis on osteoclast biology.