Bone Therapeutics Lab

Selected Publications

Munoz, M.A., Jurczyluk, J., Simon, A., Hissaria, P., Arts, R.J.W., Coman, D.J., Boros, C., Mehr, S.S. & Rogers, M.J. (2019). Defective protein prenylation in a spectrum of patients with mevalonate kinase deficiency. Frontiers in Immunology (in press).

Skinner, O.P., Jurczyluk, J., Baker, P.J., Masters, S.L., Rios Wilks, A., Clearwater, M.S., Robertson, A.A.B., Schroder, K., Mehr, S., *Munoz, M.A. & *Rogers, M.J. Lack of protein prenylation promotes NLRP3 inflammasome assembly in human monocytes. J Allergy Clin Immunol 2019; doi: 10.1016/j.jaci.2019.02.013. [Epub ahead of print].

*Munoz, M.A., *Jurczyluk, J., Mehr, S., Chai, R.C., Arts, R.J.W., Sheu, A., McMahon, C., Center, J.R., Singh-Grewal, D., Chaitow, J., Campbell, D.E., Quinn, J.M.W., Alexandrov, K., Tnimov, Z., Tangye, S.G., Simon, A., Phan, T.G. & Rogers, M.J. Defective protein prenylation is a diagnostic biomarker of mevalonate kinase deficiency. J Allergy Clin Immunol 2017; 140:873-875. doi: 10.1016/j.jaci.2017.02.033.

*Jurczyluk, J., *Munoz, M., Skinner, O.P., Chai, R.C., Ali, N., Palendira, U., Quinn, J.M.W., Preston, A., Tangye, S.G., Brown, A.J., Argent, E., Ziegler, J.B., Mehr, S. & Rogers, M.J. Mevalonate kinase deficiency leads to decreased prenylation of Rab GTPases. Immunology & Cell Biology 2016; 94:994-999.

Lawson, M., McDonald, M., Kovacic, N., Khoo, W.H., Terry, R., Down, J., Kaplan, W., Paton-Hough, J., Fellows, C., Pettitt, J., Dear, T., Van Valckenborgh, E., Baldock, P., Rogers, M.J., Eaton, C., Vanderkerken, K., Pettit, A., Quinn, J., Zannettino, A., Phan, T.G. & Croucher, P.I. Osteoclasts Control Re-activation of Dormant Myeloma Cells by Remodeling the Endosteal Niche. Nature Communications 2015; 6:8983. doi: 10.1038/ncomms9983.

Ali, N., Jurczyluk, J., Shay, G., Tnimov, Z., Alexandrov, K., Munoz, M.A., Skinner, O.P., Pavlos, N.J. & Rogers, M.J. A highly sensitive prenylation assay reveals in vivo effects of bisphosphonate drug on the Rab prenylome of macrophages outside the skeleton. Small GTPases 2015; 6:202-211.

Junankar, S., Shay, G., Jurczyluk, J., Ali, N., Down, J., Pocock, N., Parker, A., Nguyen, A., Sun, S., Kashemirov, B., McKenna, C.E., Croucher, P.I., Swarbrick, A., Weilbaecher, K. Phan, T.G. & Rogers, M.J. Real-time intravital imaging establishes tumour-associated macrophages as the extraskeletal target of bisphosphonate action in cancer. Cancer Discovery 2015; 5:35-42.

Croucher, P.I., Parker, B.S., Corcoran, N. & Rogers, M.J. Bone turnover markers and prostate cancer: not just a measure of bone disease? Eur. Urol. 2015; 68:51-52

Das, S., Edwards, P.A. Crockett, J.C. & Rogers, M.J. Upregulation of endogenous farnesyl diphosphate synthase overcomes the inhibitory effect of bisphosphonate on protein prenylation in HeLa cells. Biochim. Biophys. Acta 2014; 1841:569-73

Rumpler, M., Würger, T., Roschger, P., Zwettler, E., Sturmlechner, I., Altmann, P., Fratzl, P., Rogers, M.J., Klaushofer, K. Osteoclasts on Bone and Dentin In Vitro: Mechanism of Trail Formation and Comparison of Resorption Behavior. Calcif Tiss Int 2013; 93:526-39

Naylor AJ, Azzam E, Smith S, Croft A, Poyser C, Duffield JS, Huso DL, Gay S, Ospelt C, Cooper MS, Isacke C, Goodyear S, Rogers MJ & Buckley CD. The MSC marker CD248 (Endosialin) is a negative regulator of bone formation. Arth Rheum 2012; 64:3334-43.

Su, X., Floyd, D.H., Hughes, D., Xiang, J., Schneider, J.G., Uluckan, O., Heller, E., Deng, H., Zou, W., Craft, C.S., Wu, K., Hirbe, A.C., Grabowska, D., Eagleton, M.C., Townsley, S., Collins, L., Piwmica-Worms, D., Steinberg, T.H., Novack, D.V., Conley, P.B., Hurchla, M.A., Rogers, M. & Weilbaecher, K.N. The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodelling. J. Clin. Invest. 2012; 122:3579-3592

Moriceau, G., Roelofs, A., Brion, R., Redini, F., Ebetino, F.H., Rogers, M.J. & Heymann D. Synergistic inhibitory effect of apomine and lovastatin on osteosarcoma cell growth. Cancer 2012; 118:750-760

Whyte LS, Ford L, Ridge SA, Cameron GA, Rogers MJ & Ross RA. Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. Br J Pharmacol. 2012; 165:2584-2597

Hughes, A., Kleine-Albers, J., Helfrich, M.H., Ralston, S.H. & Rogers, M.J. A Class III Semaphorin (Sema3e) Inhibits Mouse Osteoblast Migration and Decreases Osteoclast Formation In Vitro. Calcif Tissue Int. 2012; 90:151-162

Roelofs, A.J., Stewart, C.A., Sun, S., Blazewska, K.M., Kashemirov, B.A., McKenna, C.E., Russell, R.G.G., Rogers, M.J., Lundy, M.W., Ebetino, F.H. & Coxon, F.P. Influence of bone affinity on the skeletal distribution of fluorescently-labeled bisphosphonates in vivo. J Bone Miner Res. 2012; 27:835-847.

Crockett, J.C., Mellis, D.J., Shennan, K.I.J., Duthie, A., Greenhorn, J., Wilkinson, D.I., Ralston, S.H., Helfrich, M.H. & Rogers, M.J. Signal peptide mutations in RANK prevent downstream activation of NK-kappa beta. J. Bone Miner. Res. 2011; 26:1926-1938.

Rogers, M.J., Crockett, J.C., Coxon, F.P., Monkkonen, J. Biochemical and molecular mechanisms of action of bisphosphonates. Bone 2011; 49(S1):34-41.

Itzstein C, Coxon FP, Rogers MJ. The regulation of osteoclast function and bone resorption by small GTPases. Small GTPases 2011; 2:117-130.

Taylor, A., Mules, E.H., Seabra, M., Rogers, M.J. & Coxon, F.P. Impaired prenylation of Rab GTPases in the gunmetalmouse causes defects in bone cell function. Small GTPases 2011; 2:131-142.

Coxon, F.P., Taylor, A., Stewart, C.A., Baron, R., Seabra, M, Ebetino, F.H. & Rogers, M.J. The gunmetal mouse reveals Rab geranylgeranyl transferase to be the major molecular target of phosphonocarboxylate analogues of bisphosphonates. Bone 2011; 49(S1):111-121.

Hocking, L.J., Mellis, D.J., McCabe, P.S., Helfrich, M.H. & Rogers, M.J. Functional interaction between Sequestosome-1/p62 and Autophagy-Linked FYVE-containing protein WDFY3 in human osteoclasts. Biochem Biophys Res Commun 2010; 402:543-548.

Roelofs, A.J., Coxon, F.P.; Ebetino, F.H., Lundy, M.W., Henneman, Z.J., Nancollas, G.H., Sun, S., Blazewska, K.M., Bala, J.L.F., Kashemirov, B.A., Khalid, A.B., McKenna, C.E. & Rogers, M.J. Fluorescent risedronate analogs reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo. J Bone Miner Res 2010; 25:606-616.

Russell, R.G.G., Watts, N.B., Ebetino, F.H., Rogers, M.J. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy.Osteoporos Int. 2008; 19:733-759.

Guenther, A., Gordon, S., Tiemann, M., Bakker, F., Baum, W., Burger, R., Green, J.R., Roelofs, A.J., Rogers, M.J. & Gramatzki, M. Zoledronic acid inhibits protein prenylation in non-skeletal tumours in vivo and enhances survival in the INA-6 plasmacytoma model. Int. J. Cancer 2010; 126:239-246.

Whyte, L.S., Ryberg, E., Sims, N.A., Ridge, S., Mackie, K., Greasley P.J., Ross, R.A. & Rogers, M.J. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci USA 2009; 106:16511-16516.

Sutherland, K.A., Rogers, H.L., Tosh, D. & Rogers, M.J. RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro. Arthritis Research & Therapy 2009; 11(2):R58.

Hirbe, A.C., Roelofs, A.J., Deng, H., Becker, S.N., Apicelli, A.I., Xu, Z., Prior, J.L., Piwnica-Worms, D., Rogers, M.J. & Weilbaecher, K. The bisphosphonate zoledronic acid decreases tumor growth in bone in mice with defective osteoclasts. Bone 2009; 44: 908-916.

Coxon, F.P., Thompson, K., Roelofs, A.J., Ebetino, F.H. & Rogers, M.J. Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells. Bone 2008; 42:848-860.

Sobacchi, C., Frattini, A., Guerrini, M.M., Abinun, M., Pangrazio, A., Susani, L., Bredius, R., Mancini, G., Cant, A., Bishop, N., Grabowski, P., Del Fattore, A., Messina, C., Errigo, G., Coxon, F.P., Scott, D.I., Teti, A., Rogers, M.J., Vezzoni, P., Villa, A. & Helfrich, M.H. Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nature Genetics 2007; 39:960-962.

Crockett, J.C., Schuetze, N., Tosh, D., Jatzke, S., Duthie, A., Jakob, F. & Rogers, M.J. The matricellular protein CYR61 inhibits osteoclastogenesis by a mechanism independent ofavb3 and avb5. Endocrinology 2007; 148:5761-5768.

Kavanagh, K.L., Guo, K., Dunford, J.E., Wu, X., Knapp, S., Ebetino, F.H., Rogers, M.J., Russell, R.G.G. & Oppermann, U.  The molecular mechanism of nitrogen-containing bisphosphonates as anti-osteoporosis drugs: crystal structure and inhibition of farnesyl pyrophosphate synthase. Proc. Natl. Acad. Sci USA 2006; 103:7829-7834.

Thompson, K., Rojas, J. & Rogers, M.J. Alkylamines cause Vg9Vd2-T cell activation and proliferation by inhibiting the mevalonate pathway. Blood 2006; 107:651-654.

Coxon, F.P., Ebetino, F.H., Mules, E.H., Seabra, M.C., McKenna, C. & Rogers, M.J. Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitroand in vivo. Bone 2005; 37:349-358.

Thompson, K. & Rogers, M.J. Statins prevent bisphosphonate-induced g,d-T cell proliferation and activation in vitro. J. Bone Miner. Res. 2004; 19:278-288.

Frith, J.C. & Rogers, M.J. Antagonistic effects of different classes of bisphosphonates in osteoclasts and macrophages in vitro. J. Bone Miner. Res. 2003; 18:204-212.

Coxon, F.P., Helfrich, M.H., Larijani, B., Muzylak, M., Dunford, J.E., Marshall, D., McKinnon, A.D., Nesbitt, S.A., Horton, M.A., Seabra, M.C., Ebetino, F.H. & Rogers, M.J. Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages. J. Biol. Chem. 2001; 276:48213-48222.

Frith, J.C., Monkkonen, J., Auriola, S. & Rogers, M.J. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Arth. Rheum. 2001; 44:2201-2211.

Benford, H.L., McGowan, N.W.M., Helfrich, M.H., Nuttall, M. & Rogers, M.J. Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone 2001; 28:465-473.

 Dunford, J.E., Thompson, K., Coxon, F.P., Luckman, S.P., Hahn, F.P., Poulter, C.D., Ebetino, F.H. & Rogers, M.J. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 2001; 296:235-242.


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