• Dickkopf-1 as a potential therapeutic target in Paget's disease of bone

      McCarthy, Helen S.; Marshall, Michael J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry / University of Chester ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry (Ashley, 2010-01-08)
      This article discusses Dickkopf-1 (DKK-1), which is a soluble inhibitor of Wnt signalling and its excessive expression contributes to bone loss in rheumatoid arthritis and multiple myeloma. New therapeutics have been developed for treatment of these conditions that target DKK-1 expression. DKK-1 is elevated in serum of patients with Paget's disease of the bone (PDB) and evidence is accumulating for a role of DKK-1 in PDB. At present there is no cure for PDB and the current treatment of choice are bisphosphonates. These treat the resorptive phase of PDB but do not prevent its return. This article offers a new perspective on the aetiology of PDB and speculate on DKK-1 as a therapeutic target.
    • Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells

      Humphrey, E. L.; Williams, John H. H.; Davie, Michael W. J.; Marshall, Michael J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry ; University College Chester ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry (Elsevier, 2006-05)
      This article demonstrates that dexamethasone, prednisolone, deflazacort and the dissociated glucocorticoids, RU24858, RU40066, RU24782, AL438-F1 and ZK216348 significantly inhibit osteoprotegerin (OPG) production in two human osteoblastic cell lines (MG63 and hFOB).
    • Osteoprotegerin is produced when prostaglandin synthesis is inhibited causing osteoclasts to detach from the surface of mouse parietal bone and attach to the endocranial membrane

      O’Brien, E. A.; Williams, John H. H.; Marshall, Michael J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry ; Chester College ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry (Elsevier, 2001-02-13)
      This article tests the hypothesis that osteoprotegerin (OPG) mediates the inhibition of osteoclast activity that occurs with indomethacin in the mouse calvaria.
    • Platelet-derived growth factor stimulates osteoprotegerin production in osteoblastic cells

      McCarthy, Helen S.; Williams, John H. H.; Davie, Michael W. J.; Marshall, Michael J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry / University of Chester ; University of Chester ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry (Wiley, 2008-11-20)
      This article discusses how osteoprotegerin (OPG) production by osteoblastic cells was stimulated by platelet-derived growth factor (PDGF) in two human osteosarcoma cell lines (MG63, Saos-2), a mouse pre-osteoblastic cell line (MC3T3-E1) and human bone marrow stromal cells (hMSC) by 152%, 197%, 113% and 45% respectively over 24 h. OPG was measured in the cell culture medium by immunoassay. PDGF isoforms AA, BB and AB show similar stimulation of OPG production. Message for OPG was also increased similarly to the increased secretion into the culture medium. Using specific inhibitors of cell signalling the authors demonstrate that PDGF acts through the PDGF receptor, PKC, PI3K, ERK and P38 and not via NF-kB or JNK. The importance of PDGF in fracture healing suggests a role for OPG production in countering bone resorption during the early phase of this process.
    • RANK, RANKL and osteoprotegerin in bone biology and disease

      Wright, H. L.; McCarthy, Helen S.; Middleton, Jim F.; Marshall, Michael J.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry (2008-12-20)
      This review discusses the latest news and views on the mechanisms controlling bone resorption in normal and pathological conditions.