E pathogenesis of these diseases. The most common form of bone
E pathogenesis of these diseases. The most common form of bone disease is osteoporosis, which is characterized by reduced bone mineral density (BMD) and an increased risk of fracture. Environmental factors such as diet and exercise influence BMD but genetic factors play a predominant role, accounting for up to 85 of the variation in peak BMD. Several candidate genes have been identified that regulate BMD and susceptibility to fracture, including bone morphogenic protein 2, collagen type I alpha 1, the vitamin D receptor, the estrogen receptor and lipoprotein receptor related protein 5 (LRP5). Paget’s disease of the bone (PDB) is characterised by focal abnormalities of increased bone turnover. Mutations in several genes have been identified as causes of PDB and related syndromes including receptor activator of NF-B (RANK), osteoprotegerin, sequestosome 1 and valosin containing protein. All of these genes play a role in the RANK signalling pathway, which is essential for osteoclast activation. Rare bone diseases such as osteopetrosis and hereditary osteoscleroses are also caused by mutations in genes that affect bone cell function. Osteopetrosis is characterised by increased BMD, and failure of osteoclastic bone resorption due to mutations in genes that encode proteins that are essential for osteoclast activity like the chloride pump and proton pump, or mutations in genes like cathepsin K, which breakdown bone matrix. Although the bones are dense, fractures are common in osteopetrosis because of reduced bone quality. Osteosclerosis occurs because of mutations in genes that increase osteoblast activity, including SOST, transforming growth factor beta and LRP5. Osteosclerotic patients also have increased BMD but fractures PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27324125 are rare, because bone quality is normal. From a clinical standpoint, advances in knowledge about the genetic basis of bone disease offers the prospect of developing new markers for assessing fracture risk and the identification of new molecular targets that will form the basis for the design of new treatments.6.F, Amara A, Curnow SJ, Lord JM, Scheel-Toellner D, Salmon M: Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium. J Immunol 2000, 165:3423-3429. Buckley CD: Why do leucocytes accumulate within chronically buy RG7800 inflamed joints? Rheumatology 2003, 42:1433-1444. Amft N, Curnow SJ, Scheel-Toellner D, Devadas A, Oates J, Crocker J, Hamburger J, Ainsworth J, Mathews J, Salmon M, et al.: Ectopic PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25636517 expression of the B cell attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sj ren’s Syndrome. Arthritis Rheum 2001, 44:2633-2641. Parsonage G, Falciani F, Burman A, Filer A, Ross E, Bofill M, Martin S, Salmon M, Buckley CD: Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns. Thromb Haemost 2003, 90:688-697.S15 Regulating apoptosis in fibroblastsT Pap1, A Cinski2, A Drynda2, A Wille2, A Baier2, S Gay3, I Meinecke4 1Division of Molecular Medicine of Musculoskeletal Tissue, University Hospital, Munster, Germany; 2Division of Experimental Rheumatology, University Hospital Magdeburg, Germany; 3Center of Experimental Rheumatology, Department of Rheumatology, University Hospital, Zurich, Switzerland; 4Department of Traumatology, Hand and Recon.