• A bio-assay for effectors of osteoclast differentiation in serum from patients with bone disease

      Dugard, Marit-Naomi; Sharp, Christopher A.; Evans, Sally F.; 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 ; 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 ; 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 (Elsevier, 2005-06)
      Osteoclast differentiation and activity, and hence bone loss, depend on two opposing cytokines. Receptor activator of NF-κB ligand (RANKL) produced by osteoblasts and T-cells stimulates, while osteoprotegerin inhibits. Both of these cytokines are found in serum. Our aim was to develop a functional assay for any factors present in human serum that can affect osteoclast differentiation and to assess whether any such factors vary in diseases in which bone loss occurs.
    • Bone extracts can stimulate the secrtion of osteoprotegerin in the osteosarcoma cell lines MG-63 and SAOS-2

      Powell, Diane E.; Johnson, William Eustace Basil; Marshall, Michael J.; Williams, John H. H.; Davie, Michael W. J. (American Society for Bone and Mineral Research, 2005)
    • 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).
    • Increased circulating Dickkopf-1 in Paget's disease of bone

      Marshall, Michael J.; Evans, Sally F.; Sharp, Christopher A.; Powell, Diane E.; McCarthy, Helen S.; Davie, Michael W. 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 (Elsevier, 2009-07)
      This article discusses Dickkopf-1 (Dkk-1), which is a secreted inhibitor of Wnt signaling which in adults regulates bone turnover. Dkk-1 over-production is implicated in osteolytic disease where it inhibits bone formation and stimulates bone breakdown. Recently it was reported that osteoblastic cells from Paget's disease of bone (PDB) over-expressed Dkk-1. This study aimed yo see if increased Dkk-1 was detected in serum from patients with PDB. The results showed that Dkk-1 and total serum alkaline phosphatase activity (tsAP) were significantly elevated in sera from PDB patients. Patients with polyostotic PDB had significantly higher levels of tsAP but not Dkk-1, than monostotic patients. TsAP but not Dkk-1, was significantly lower in sera from bisphosphonate treated versus untreated PDB patients. Dkk-1 and tsAP were not significantly correlated. Dkk-1 may be a useful biomarker of PDB and the authors speculate that Dkk-1 may play a central role in the etiology of PDB.
    • 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.
    • Regional differences in mechanical and material properties of femoral head cancellous bone in health and osteoarthritis

      Brown, Sharon J.; Pollintine, Phillip; Powell, Diane E.; Davie, Michael W. J.; Sharp, Christopher A.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry/Chester College of Higher Education ; 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 ; 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 (Springer, 2002-09)
      Osteoarthritis (OA) is a debilitating condition common among the aging population. In this study we have determined mechanical and material properties of cancellous bone cores from two differently loaded regions of femoral heads obtained from healthy subjects and those with end-stage osteoarthritis. Densitometric properties were determined prior to compression testing for Young's modulus (EC) and yield strength (sy), after which bones were powdered for analysis of collagen and mineral content. In both OA and normal cancellous bone, volumetric bone mineral density (BMDv), apparent density (rA), EC, and sy were systematically greater in the superior than in the inferior region (P<0.05). In the OA inferior region, median BMDv (0.434 g-cm-3) and rA (0.426 g-cm-3) were significantly greater than in normals (0.329 and 0.287 g-cm-3, respectively, both P<0.05) reflecting an increased amount of tissue. The mineral:collagen ratio was decreased in OA, but this was only significant in the superior region (P<0.008). Relationships between EC and both BMDv and rA were weaker in OA bone cores (r2 = 0.66 and r2 = 0.59) than in normals (r2 = 0.86 and r2 = 0.77, respectively). Likewise, sy and both BMDv and rA were weaker in OA (r2 = 0.74 and r2 = 0.70) than in normals (r2 = 0.83 and r2 = 0.77, respectively). For the same value of density measure, EC and sy tended to be lower in OA bone when compared with normal bone. In conclusion, femoral head cancellous bone mass in end-stage osteoarthritis is increased but undermineralized, and is neither stiffer nor stronger than normal cancellous bone.