Fm Collier
University of Melbourne
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Publication
Featured researches published by Fm Collier.
Journal of Bone and Mineral Research | 2002
Wayne R. Holloway; Fm Collier; C. J. Aitken; Damian E. Myers; Jason M. Hodge; Mary Malakellis; Tamara J. Gough; Gregory Collier; Geoffrey C. Nicholson
Originally, leptin was described as a product of adipocytes that acts on the hypothalamus to regulate appetite. However, subsequently, it has been shown that leptin receptors are distributed widely and that leptin has diverse functions, including promotion of hemopoietic and osteoblastic differentiation. It has been recognized for some time that both serum leptin and bone mass are correlated positively to body fat mass and, recently, we have shown a direct positive relationship between serum leptin and bone mass in nonobese women. We now report that leptin inhibits osteoclast generation in cultures of human peripheral blood mononuclear cells (PBMCs) and murine spleen cells incubated on bone in the presence of human macrophage colony‐stimulating factor (hM‐CSF) and human soluble receptor activator of NF‐κB ligand (sRANKL). The half‐maximal concentration inhibitory of leptin was approximately 20 nM in the presence of sRANKL at 40 ng/ml but decreased to approximately 2 nM when sRANKL was used at 5 ng/ml. The majority of the inhibitory effect occurred in the first week of the 3‐week cultures. Inhibition did not occur when the PBMC cultures were washed vigorously to remove nonadherent cells or when purified CD14+ monocytes were used to generate osteoclasts, indicating an indirect or permissive effect via CD14− PBMC. Leptin increased osteoprotegerin (OPG) messenger RNA (mRNA) and protein expression in PBMC but not in CD14+ cells, suggesting that the inhibitory effect may be mediated by the RANKL/RANK/OPG system. Leptin may act locally to increase bone mass and may contribute to linkage of bone formation and resorption.
Bone | 1996
Wayne R. Holloway; Fm Collier; Re Herbst; Jason M. Hodge; Geoffrey C. Nicholson
Zinc is an important element in biology yet little is understood of its role in bone cell metabolism and function. This study examined the effects of zinc on osteoclast (OC) function in cultures derived from neonatal rats and in cocultures of OC and UMR 106-01 osteoblast-like cells (UMR/OC cocultures). Treatment with zinc (10(-12)-10(-4) mol/L) had no effect on either bone resorption or the number of multinucleate cells positive for tartrate-resistant acid phosphatase (TRACP + ve MNC) in OC cultured for 24 h on bone slices. However, in UMR/OC cocultures, 10(-4) mol/L zinc (but not lower concentrations) decreased resorption pit formation by approximately 50% and increased TRACP + ve MNC number by approximately 40%. When osteoblast-like cells were pretreated with zinc prior to, but not during, coculture with OC, effects on TRACP + ve MNC and pit number persisted, although the effect was reduced. Zinc treatment also inhibited resorption and stimulated TRACP and calcitonin receptor (CTR) + ve MNC numbers in long-term (96-120 h) UMR/OC cocultures. Our results indicate that zinc increases TRACP + ve CTR + ve MNC numbers yet inhibits bone-resorbing activity, and that these effects are dependent on the presence of osteoblastic cells. Zinc is abundant in bone and may act as a local regulator of bone cells.
Osteoporosis International | 2011
Tania J. Fernandes; Fm Collier; Jason M. Hodge; Mark A. Kirkland; Geoffrey C. Nicholson
The extracellular calcium-sensing receptor (CaR) is a class C G Protein-Coupled Receptor (GPCR) with multimodal sensing properties. The CaR responds to multivalent cation agonists including Ca, Mg and Gd and is subject to allosteric modulation by L-amino acids, glutathione and its analog S-methylglutathione (SMG) that bind in the Venus Fly Trap domain as well as phenylalkylamines including NPS R-467 and Cinacalcet that bind in the heptahelical domains. The CaR couples to the heterotrimeric G-proteins Gq/11, Gi/o & G12/13 resulting in the activation of various signalling pathways leading to intracellular calcium mobilization, ERK1/2 activation and suppression of cAMP levels. In the present study, we show that CaR-mediated suppression of cAMP arises from both a reduction in synthesis by adenylyl cyclases and enhanced degradation by phosphodiesterases. Real-time measurement of changes in intracellular cAMP levels was achieved using the cAMP biosensor CFPnd-Epac1-cpVenus in a Fluorescence Resonance Energy Transfer (FRET)-based microfluorescence assay. EPac is a guanine nucleotide exchange protein directly activated by cAMP. All allosteric modulators tested including L-Phenylalanine, SMG and cinacalcet enhanced extracellular calcium Ca2þ o induced decreases in cAMP levels. Overnight treatment of cells with pertussis toxin, an inhibitor of Gi/o, abolished not only Ca 2þ o mediated cAMP inhibition but also the effects of the allosteric modulators suggesting that Gi/o activation is critical to the receptor ’s control of cAMP levels. Isobutyl Methyl Xanthine (IBMX), a phosphodiesterase (PDE) inhibitor significantly reduced the potency ofCa2þ o . The results suggest that CaR mediated reduction in cAMP is dependent on inactivation of adenylyl cyclase via Gi/o and supported by PDE activation.
Osteoporosis International | 2011
Jason M. Hodge; Yuanyuan Wang; Lana J. Williams; Fm Collier; Tania J. Fernandes; Matthew J. Constable; Julie A. Pasco; Seetal Dodd; Geoffrey C. Nicholson; Michael Berk
6 ANDROGENS ARE CRITICALTO NEUROPEPTIDE Y MEDIATED CONTROL OF BONE FORMATION A. Zengin,R.F. Enriquez,A.D. Nguyen,N.J. Lee,A. Sainsbury,H. Herzog,J.A. Eisman,P.A. Baldock Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Neuroscience Program, Garvan Institute of Medical Research, Faculty of Medicine, University of New SouthWales, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
Clinical Science | 2000
Geoffrey C. Nicholson; Mary Malakellis; Fm Collier; Paul U. Cameron; Wayne R. Holloway; Tamara J. Gough; Claudia C. Gregorio-King; Mark A. Kirkland; Damian E. Myers
Endocrinology | 1998
Fm Collier; Wen Hua Huang; Wayne R. Holloway; Jason M. Hodge; Matthew T. Gillespie; Ll Daniels; Ming-Hao Zheng; Geoffrey C. Nicholson
Calcified Tissue International | 1997
Wayne R. Holloway; Fm Collier; Re Herbst; Jason M. Hodge; Geoffrey C. Nicholson
Bone | 2001
Geoffrey C. Nicholson; C. J. Aitken; Jason M. Hodge; Wayne R. Holloway; Tamara J. Gough; Fm Collier; Mark A. Kirkland; Damian E. Myers
Journal of Bone and Mineral Research | 1999
Damian E. Myers; Fm Collier; C. Minkin; Wayne R. Holloway; H. Wang; Mary Malakellis; Geoffrey C. Nicholson
Journal of Bone and Mineral Research | 1997
Jason M. Hodge; Re Herbst; Wh Huang; Wayne R. Holloway; Ll Daniels; Fm Collier; M.H. Zheng; Geoffrey C. Nicholson