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Charles O'Brien

TitleProfessor
InstitutionUniversity of Arkansas for Medical Sciences
DepartmentInternal Med, College of Medicine
DivisionInternal Med Endo
Address834 Cancer Institute
4104 Outpatient Circle
Mail Slot # 587
Little Rock AR 72205
Phone501-686-5607
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    Other Positions
    TitleProfessor
    InstitutionUniversity of Arkansas for Medical Sciences
    DepartmentOrthopaedics, College of Medicine


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    1. Piemontese M, Almeida M, Robling AG, Kim HN, Xiong J, Thostenson JD, Weinstein RS, Manolagas SC, O'Brien CA, Jilka RL. Old age causes de novo intracortical bone remodeling and porosity in mice. JCI Insight. 2017 Sep 07; 2(17). PMID: 28878136.
      View in: PubMed
    2. Lee SM, Meyer MB, Benkusky NA, O'Brien CA, Pike JW. The impact of VDR expression and regulation in vivo. J Steroid Biochem Mol Biol. 2017 Jun 09. PMID: 28602960.
      View in: PubMed
    3. Kim HN, Chang J, Shao L, Han L, Iyer S, Manolagas SC, O'Brien CA, Jilka RL, Zhou D, Almeida M. DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age. Aging Cell. 2017 Aug; 16(4):693-703. PMID: 28401730.
      View in: PubMed
    4. Fil D, DeLoach A, Yadav S, Alkam D, MacNicol M, Singh A, Compadre CM, Goellner JJ, O'Brien CA, Fahmi T, Basnakian AG, Calingasan NY, Klessner JL, Beal FM, Peters OM, Metterville J, Brown RH, Ling KKY, Rigo F, Ozdinler PH, Kiaei M. Mutant Profilin1 transgenic mice recapitulate cardinal features of motor neuron disease. Hum Mol Genet. 2017 Feb 15; 26(4):686-701. PMID: 28040732.
      View in: PubMed
    5. Almeida M, Laurent MR, Dubois V, Claessens F, O'Brien CA, Bouillon R, Vanderschueren D, Manolagas SC. Estrogens and Androgens in Skeletal Physiology and Pathophysiology. Physiol Rev. 2017 01; 97(1):135-187. PMID: 27807202.
      View in: PubMed
    6. Ucer S, Iyer S, Kim HN, Han L, Rutlen C, Allison K, Thostenson JD, de Cabo R, Jilka RL, O'Brien C, Almeida M, Manolagas SC. The Effects of Aging and Sex Steroid Deficiency on the Murine Skeleton Are Independent and Mechanistically Distinct. J Bone Miner Res. 2017 Mar; 32(3):560-574. PMID: 27714847.
      View in: PubMed
    7. Piemontese M, Xiong J, Fujiwara Y, Thostenson JD, O'Brien CA. Cortical bone loss caused by glucocorticoid excess requires RANKL production by osteocytes and is associated with reduced OPG expression in mice. Am J Physiol Endocrinol Metab. 2016 Sep 01; 311(3):E587-93. PMID: 27460899.
      View in: PubMed
    8. Piemontese M, Onal M, Xiong J, Han L, Thostenson JD, Almeida M, O'Brien CA. Low bone mass and changes in the osteocyte network in mice lacking autophagy in the osteoblast lineage. Sci Rep. 2016 Apr 11; 6:24262. PMID: 27064143; PMCID: PMC4827128.
    9. Liu Y, Almeida M, Weinstein RS, O'Brien CA, Manolagas SC, Jilka RL. Skeletal inflammation and attenuation of Wnt signaling, Wnt ligand expression, and bone formation in atherosclerotic ApoE-null mice. Am J Physiol Endocrinol Metab. 2016 May 01; 310(9):E762-73. PMID: 26956187.
      View in: PubMed
    10. Jilka RL, O'Brien CA. The Role of Osteocytes in Age-Related Bone Loss. Curr Osteoporos Rep. 2016 Feb; 14(1):16-25. PMID: 26909563.
      View in: PubMed
    11. Lee SM, Meyer MB, Benkusky NA, O'Brien CA, Pike JW. Mechanisms of Enhancer-mediated Hormonal Control of Vitamin D Receptor Gene Expression in Target Cells. J Biol Chem. 2015 Dec 18; 290(51):30573-86. PMID: 26504088; PMCID: PMC4683277 [Available on 12/18/16].
    12. Xiong J, Piemontese M, Onal M, Campbell J, Goellner JJ, Dusevich V, Bonewald L, Manolagas SC, O'Brien CA. Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone. PLoS One. 2015; 10(9):e0138189. PMID: 26393791; PMCID: PMC4578942.
    13. Kim HN, Han L, Iyer S, de Cabo R, Zhao H, O'Brien CA, Manolagas SC, Almeida M. Sirtuin1 Suppresses Osteoclastogenesis by Deacetylating FoxOs. Mol Endocrinol. 2015 Oct; 29(10):1498-509. PMID: 26287518; PMCID: PMC4588729 [Available on 10/01/16].
    14. Ucer S, Iyer S, Bartell SM, Martin-Millan M, Han L, Kim HN, Weinstein RS, Jilka RL, O'Brien CA, Almeida M, Manolagas SC. The Effects of Androgens on Murine Cortical Bone Do Not Require AR or ERa Signaling in Osteoblasts and Osteoclasts. J Bone Miner Res. 2015 Jul; 30(7):1138-49. PMID: 25704845; PMCID: PMC4871247.
    15. Onal M, Bishop KA, St John HC, Danielson AL, Riley EM, Piemontese M, Xiong J, Goellner JJ, O'Brien CA, Pike JW. A DNA segment spanning the mouse Tnfsf11 transcription unit and its upstream regulatory domain rescues the pleiotropic biologic phenotype of the RANKL null mouse. J Bone Miner Res. 2015 May; 30(5):855-68. PMID: 25431114.
      View in: PubMed
    16. Piemontese M, Onal M, Xiong J, Wang Y, Almeida M, Thostenson JD, Weinstein RS, Manolagas SC, O'Brien CA. Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone. Bone. 2015 Jun; 75:18-26. PMID: 25700544; PMCID: PMC4387016.
    17. Lee SM, Goellner JJ, O'Brien CA, Pike JW. A humanized mouse model of hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia. Endocrinology. 2014 Nov; 155(11):4137-48. PMID: 25147982; PMCID: PMC4197979.
    18. Iyer S, Han L, Bartell SM, Kim HN, Gubrij I, de Cabo R, O'Brien CA, Manolagas SC, Almeida M. Sirtuin1 (Sirt1) promotes cortical bone formation by preventing ß-catenin sequestration by FoxO transcription factors in osteoblast progenitors. J Biol Chem. 2014 Aug 29; 289(35):24069-78. PMID: 25002589; PMCID: PMC4148840.
    19. Xiong J, Piemontese M, Thostenson JD, Weinstein RS, Manolagas SC, O'Brien CA. Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone. 2014 Sep; 66:146-54. PMID: 24933342; PMCID: PMC4125539.
    20. Bartell SM, Kim HN, Ambrogini E, Han L, Iyer S, Serra Ucer S, Rabinovitch P, Jilka RL, Weinstein RS, Zhao H, O'Brien CA, Manolagas SC, Almeida M. FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation. Nat Commun. 2014 Apr 30; 5:3773. PMID: 24781012; PMCID: PMC4015330.
    21. Lee SM, Bishop KA, Goellner JJ, O'Brien CA, Pike JW. Mouse and human BAC transgenes recapitulate tissue-specific expression of the vitamin D receptor in mice and rescue the VDR-null phenotype. Endocrinology. 2014 Jun; 155(6):2064-76. PMID: 24693968; PMCID: PMC4020932.
    22. Jilka RL, O'Brien CA, Roberson PK, Bonewald LF, Weinstein RS, Manolagas SC. Dysapoptosis of osteoblasts and osteocytes increases cancellous bone formation but exaggerates cortical porosity with age. J Bone Miner Res. 2014 Jan; 29(1):103-17. PMID: 23761243; PMCID: PMC3823639.
    23. Iyer S, Ambrogini E, Bartell SM, Han L, Roberson PK, de Cabo R, Jilka RL, Weinstein RS, O'Brien CA, Manolagas SC, Almeida M. FOXOs attenuate bone formation by suppressing Wnt signaling. J Clin Invest. 2013 Aug; 123(8):3409-19. PMID: 23867625; PMCID: PMC3726166.
    24. Almeida M, O'Brien CA. Basic biology of skeletal aging: role of stress response pathways. J Gerontol A Biol Sci Med Sci. 2013 Oct; 68(10):1197-208. PMID: 23825036; PMCID: PMC3779633.
    25. O'Brien CA, Nakashima T, Takayanagi H. Osteocyte control of osteoclastogenesis. Bone. 2013; 54(2):258-63.
    26. Jilka RL, O'Brien CA, Roberson PK, Bonewald LF, Weinstein RS, Manolagas SC. Dysapoptosis of osteoblasts and osteocytes increases cancellous bone formation but exaggerates bone porosity with age. J Bone Mineral Res. 2013.
    27. Onal M, Piemontese M, Xiong J, Wang Y, Han L, Ye S, Komatsu M, Selig M, Weinstein RS, Zhao H, Jilka RL, Almeida M, Manolagas SC, O'Brien CA. Suppression of autophagy in osteocytes mimics skeletal aging. J Biol Chem. 2013 Jun 14; 288(24):17432-40. PMID: 23645674; PMCID: PMC3682543.
    28. Almeida M, Iyer S, Martin-Millan M, Bartell SM, Han L, Ambrogini E, Onal M, Xiong J, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC. Estrogen receptor-alpha signaling in osteoblast progenitors stimulates cortical bone accrual. J Clin Invest. 2013; 123(1):394 - 404.
    29. Almeida M, Iyer S, Martin-Millan M, Bartell SM, Han L, Ambrogini E, Onal M, Xiong J, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC. Estrogen receptor-a signaling in osteoblast progenitors stimulates cortical bone accrual. J Clin Invest. 2013 Jan; 123(1):394-404. PMID: 23221342; PMCID: PMC3533305.
    30. O'Brien CA, Nakashima T, Takayanagi H. Osteocyte control of osteoclastogenesis. Bone. 2013 Jun; 54(2):258-63. PMID: 22939943; PMCID: PMC3538915.
    31. Onal M, Xiong J, Chen X, Thostenson JD, Almeida M, Manolagas SC, O'Brien CA. Receptor activator of nuclear factor kappaB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem. 2012; 287(35):29851 - 29860.
    32. Onal M, Xiong J, Chen X, Thostenson JD, Almeida M, Manolagas SC, O'Brien CA. Receptor activator of nuclear factor ?B ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem. 2012 Aug 24; 287(35):29851-60. PMID: 22782898; PMCID: PMC3436192.
    33. Xiong J, O'Brien CA. Osteocyte RANKL: new insights into the control of bone remodeling. J Bone Miner Res. 2012; 27(3):499 - 505.
    34. Onal M, Galli C, Fu Q, Xiong J, Weinstein RS, Manolagas SC, O'Brien CA. The RANKL distal control region is required for the increase in RANKL expression, but not the bone loss, associated with hyperparathyroidism or lactation in adult mice. Mol Endocrinol. 2012 Feb; 26(2):341-8. PMID: 22207718; PMCID: PMC3275157.
    35. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011 Sep 11; 17(10):1235-41. PMID: 21909103; PMCID: PMC3192296.
    36. Weinstein RS, O'Brien CA, Almeida M, Zhao H, Roberson PK, Jilka RL, Manolagas SC. Osteoprotegerin prevents glucocorticoid-induced osteocyte apoptosis in mice. Endocrinology. 2011 Sep; 152(9):3323-31. PMID: 21771887; PMCID: PMC3159783.
    37. Rhee Y, Allen MR, Condon K, Lezcano V, Ronda AC, Galli C, Olivos N, Passeri G, O'Brien CA, Bivi N, Plotkin LI, Bellido T. PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling. J Bone Miner Res. 2011 May; 26(5):1035-46. PMID: 21140374; PMCID: PMC3179307.
    38. Jilka RL, O'Brien CA, Bartell SM, Weinstein RS, Manolagas SC. Continuous elevation of PTH increases the number of osteoblasts via both osteoclast-dependent and -independent mechanisms. J Bone Miner Res. 2010 Nov; 25(11):2427-37. PMID: 20533302; PMCID: PMC3179285.
    39. Almeida M, Martin-Millan M, Ambrogini E, Bradsher R, Han L, Chen XD, Roberson PK, Weinstein RS, O'Brien CA, Jilka RL, Manolagas SC. Estrogens attenuate oxidative stress and the differentiation and apoptosis of osteoblasts by DNA-binding-independent actions of the ERalpha. J Bone Miner Res. 2010 Apr; 25(4):769-81. PMID: 19821774; PMCID: PMC3153331.
    40. O'Brien CA. Control of RANKL gene expression. Bone. 2010; 46(4):911 - 919.
    41. Ambrogini E, Almeida M, Martin-Millan M, Paik JH, Depinho RA, Han L, Goellner J, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC. FoxO-mediated defense against oxidative stress in osteoblasts is indispensable for skeletal homeostasis in mice. Cell Metab. 2010 Feb 03; 11(2):136-46. PMID: 20142101; PMCID: PMC2819984.
    42. Martin-Millan M, Almeida M, Ambrogini E, Han L, Zhao H, Weinstein RS, Jilka RL, O'Brien CA, Manolagas SC. The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol. 2010 Feb; 24(2):323-34. PMID: 20053716; PMCID: PMC2817608.
    43. O'Brien,CA. Control of RANKL gene expression. Bone. 2010; 46:911-919.
    44. Weinstein RS, Wan C, Liu Q, Wang Y, Almeida M, O'Brien CA, Thostenson J, Roberson PK, Boskey AL, Clemens TL, Manolagas SC. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice. Aging Cell. 2010 Apr; 9(2):147-61. PMID: 20047574; PMCID: PMC2858771.
    45. O'Brien CA. Control of RANKL gene expression. Bone. 2010 Apr; 46(4):911-9. PMID: 19716455; PMCID: PMC2842447.
    46. Galli C, Fu Q, Wang W, Olsen BR, Manolagas SC, Jilka RL, O'Brien CA. Commitment to the osteoblast lineage is not required for RANKL gene expression. J Biol Chem. 2009 May 08; 284(19):12654-62. PMID: 19279010; PMCID: PMC2675994.
    47. Jilka RL, O'Brien CA, Ali AA, Roberson PK, Weinstein RS, Manolagas SC. Intermittent PTH stimulates periosteal bone formation by actions on post-mitotic preosteoblasts. Bone. 2009 Feb; 44(2):275-86. PMID: 19010455; PMCID: PMC2655212.
    48. O'Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, Robling AG, Bouxsein M, Schipani E, Turner CH, Jilka RL, Weinstein RS, Manolagas SC, Bellido T. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One. 2008 Aug 13; 3(8):e2942. PMID: 18698360; PMCID: PMC2491588.
    49. Galli C, Zella LA, Fretz JA, Fu Q, Pike JW, Weinstein RS, Manolagas SC, O'Brien CA. Targeted deletion of a distant transcriptional enhancer of the receptor activator of nuclear factor-kappaB ligand gene reduces bone remodeling and increases bone mass. Endocrinology. 2008 Jan; 149(1):146-53. PMID: 17932217; PMCID: PMC2194617.
    50. Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem. 2007 Sep 14; 282(37):27298-305. PMID: 17623658.
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    51. Almeida M, Han L, Martin-Millan M, Plotkin LI, Stewart SA, Roberson PK, Kousteni S, O'Brien CA, Bellido T, Parfitt AM, Weinstein RS, Jilka RL, Manolagas SC. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem. 2007 Sep 14; 282(37):27285-97. PMID: 17623659; PMCID: PMC3119455.
    52. Aguirre JI, Plotkin LI, Gortazar AR, Millan MM, O'Brien CA, Manolagas SC, Bellido T. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J Biol Chem. 2007 Aug 31; 282(35):25501-8. PMID: 17609204.
      View in: PubMed
    53. Manolagas SC, Jilka RL, Kousteni S, Bellido T, Weinstein RS, O'Brien CA, Plotkin L, Han L. Response to Windahl et al. J Clin Invest. 2006 Nov; 116(11):2834. PMID: 17080186; PMCID: PMC1626133.
    54. Fu Q, Manolagas SC, O'Brien CA. Parathyroid hormone controls receptor activator of NF-kappaB ligand gene expression via a distant transcriptional enhancer. Mol Cell Biol. 2006 Sep; 26(17):6453-68. PMID: 16914731; PMCID: PMC1592840.
    55. O'Brien CA, Jilka RL, Fu Q, Stewart S, Weinstein RS, Manolagas SC. IL-6 is not required for parathyroid hormone stimulation of RANKL expression, osteoclast formation, and bone loss in mice. Am J Physiol Endocrinol Metab. 2005 Nov; 289(5):E784-93. PMID: 15956054.
      View in: PubMed
    56. O'Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology. 2004 Apr; 145(4):1835-41. PMID: 14691012.
      View in: PubMed
    57. Bellido T, Ali AA, Plotkin LI, Fu Q, Gubrij I, Roberson PK, Weinstein RS, O'Brien CA, Manolagas SC, Jilka RL. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem. 2003 Dec 12; 278(50):50259-72. PMID: 14523023.
      View in: PubMed
    58. Fu Q, Jilka RL, Manolagas SC, O'Brien CA. Parathyroid hormone stimulates receptor activator of NFkappa B ligand and inhibits osteoprotegerin expression via protein kinase A activation of cAMP-response element-binding protein. J Biol Chem. 2002 Dec 13; 277(50):48868-75. PMID: 12364326.
      View in: PubMed
    59. O'Brien CA, Kern B, Gubrij I, Karsenty G, Manolagas SC. Cbfa1 does not regulate RANKL gene activity in stromal/osteoblastic cells. Bone. 2002 Mar; 30(3):453-62. PMID: 11882458.
      View in: PubMed
    60. Shi H, O'Brien CA, Van Horn DJ, Wolin SL. A misfolded form of 5S rRNA is complexed with the Ro and La autoantigens. RNA. 1996; 2(8):769 - 784.
    61. Manolagas SC, Jilka RL, Bellido T, O'Brien CA, Parfitt, AM. Principles of bone biology. Interleukin-6-type cytokines and their receptors. 1996.
    62. Ge Q, Nilasena DS, O'Brien CA, Frank MB, Targoff IN. Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen. J Clin Invest. 1995; 96(4):1730 - 1737.
    63. Van Horn DJ, Eisenberg D, O'Brien CA, Wolin SL. Caenorhabditis elegans embryos contain only one major species of Ro RNP. RNA. 1995; 1(3):293 - 303.
    64. Farris AD, O'Brien CA, Harley JB. Y3 is the most conserved small RNA component of Ro ribonucleoprotein complexes in vertebrate species. Gene. 1995; 154(2):193 - 198.
    65. O'Brien CA, Wolin SL. A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors. Genes Dev. 1994; 8(23):2891 - 2903.
    66. O'Brien CA, Margelot K, Wolin SL. Xenopus Ro ribonucleoproteins: members of an evolutionarily conserved class of cytoplasmic ribonucleoproteins. Proc Natl Acad Sci U S A. 1993; 90(15):7250 - 7254.
    67. Ge Q, Frank MB, O'Brien C, Targoff IN. Cloning of a complementary DNA coding for the 100-kD antigenic protein of the PM-Scl autoantigen. J Clin Invest. 1992; 90(2):559 - 570.
    68. O'Brien CA, Harley JB. Association of hY4 pseudogenes with Alu repeats and abundance of hY RNA-like sequences in the human genome. Gene. 1992; 116(2):285 - 289.
    69. O'Brien CA, Harley JB. A subset of hY RNAs is associated with erythrocyte Ro ribonucleoproteins. EMBO J. 1990; 9(11):3683 - 3689.
    70. James JA, Dickey WD, Fujisaku A, O'Brien CA, Deutscher SL, Keene JD, Harley JB. Antigenicity of a recombinant Ro (SS-A) fusion protein. Arthritis Rheum. 1990; 33(1):102 - 106.
    71. Mamula MJ, O'Brien CA, Harley JB, Hardin JA. The Ro ribonucleoprotein particle: induction of autoantibodies and the detection of Ro RNAs among species. Clin Immunol Immunopathol. 1989; 52(3):435 - 446.
    72. Targoff IN, Arnett FC, Berman L, O'Brien C, Reichlin M. Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease. J Clin Invest. 1989; 84(1):162 - 172.
    73. Rader MD, O'Brien C, Liu YS, Harley JB, Reichlin M. Heterogeneity of the Ro/SSA antigen. Different molecular forms in lymphocytes and red blood cells. J Clin Invest. 1989; 83(4):1293 - 1298.
    74. Jilka RL, Bellido T, Almeida M, Plotkin LI, O'Brien CA, Weinstein RS, Manolagas SC. Principles of bone biology. Apoptosis of Bone Cells.
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