Location of Repository

Glucocorticoid-Induced Osteoporosis – A Disorder of Mesenchymal Stromal Cells?

By Rowan Hardy and Mark S. Cooper

Abstract

Glucocorticoids are a class of steroid hormones that are essential to life but cause serious harm in excess. The main clinical features of glucocorticoid excess are due to adverse effects on cells and tissues that arise from a common developmental precursor – the mesenchymal stromal cell (MSC; sometimes referred to as the mesenchymal stem cell). Interestingly glucocorticoids appear essential for the differentiation of cells and tissues that arise from MSCs. High levels of glucocorticoids are used in tissue engineering strategies to enhance the formation of tissues such as bone, cartilage, and muscle. This article discusses the paradox that glucocorticoids both enhance and impair MSC development and function. It will describe how endogenous glucocorticoids are likely to be important in these processes in vivo and will discuss the implications for therapies aimed at reducing the damage associated with the use of therapeutic glucocorticoids

Topics: Endocrinology
Publisher: Frontiers Research Foundation
OAI identifier: oai:pubmedcentral.nih.gov:3356084
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Preview

    Citations

    1. (2001). 11 Beta-hydroxysteroid dehydrogenase type 1 is induced in human monocytes upon differentiation to macrophages.
    2. (2007). 11BetaHSD type 1 expression in human adipose tissue: impact of gender, obesity, and fat localization.
    3. (2005). 11β-Hydroxysteroid dehydrogenase expression and glucocorticoid synthesis are directed by a molecular switch during osteoblast differentiation.
    4. (2011). 7Hardy and Cooper Glucocorticoids and stromal
    5. (1994). A meta-analysis of the effect of oral and inhaled corticosteroids on growth.
    6. (1998). A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo.
    7. (2005). A stromal address code defined by fibroblasts.
    8. (2010). Adrenal gland and bone.
    9. and Asadullah,K.(2006).Glucocorticoid therapy-induced skin atrophy.
    10. and Shinomiya,K.(2007).Effectsof continuous dexamethasone treatment on differentiation capabilities of bone marrow-derived mesenchymal cells.
    11. andStewart,P.M.(2002).Osteoblastic 11β-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid
    12. (2005). Antiinflammatory action of glucocorticoids – new mechanisms for old drugs.
    13. (2006). Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1.
    14. (1992). Characterization of cells with osteogenic potential from human marrow.
    15. (2006). Characterization of the metabolic phenotypes of Cushing’s syndrome and growth hormonedeficiency:astudyof body composition and energy metabolism.
    16. (1998). Chondrogenicdifferentiationofcultured human mesenchymal stem cells from marrow.
    17. (2009). Clinical features associated with glucocorticoid receptor polymorphisms. An overview.
    18. (2010). Conversion of vascular endothelial cells into multipotent stem-like cells.
    19. Cooper,M.S.(2004).Sensitivityofbone to glucocorticoids.
    20. (2003). Corticosteroid insufficiency inacutelyillpatients.N.Engl.J.Med. 348, 727–734. Cooper,M.S.,andStewart,P.M.(2009). 11Beta-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus-pituitary-adrenal axis, metabolic syndrome, and inflammation.
    21. (2005). Cortisol secretion and rate of bone loss in a population-based cohort of elderly men and women.
    22. (2009). dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.
    23. (2006). Depletion of resting zone chondrocytes during growth plate senescence.
    24. (2006). Differentialexpression,functionand response to inflammatory stimuli of 11β-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulationofinflammation.ArthritisRes.
    25. (1999). Differentiation of adipose stromal cells: the roles of glucocorticoids and 11β-hydroxysteroid dehydrogenase.
    26. (1997). Does central obesity reflect “Cushing’s disease of the omentum?”
    27. (1972). Effect of catecholamines and dibutyryl-cyclic-AMP on glucoseturnover,plasmafreefattyacids, and insulin in dogs treated with methylprednisolone.
    28. (1993). Effects of adrenalectomy or RU-486 on rat muscle fibers during hindlimb suspension.
    29. (1996). Effects of gender and ageonthelevelsandcircadianrhythmicity of plasma cortisol.
    30. (2009). Endogenous glucocorticoids and impaired insulin signaling are both required to stimulate muscle wasting under pathophysiological conditions in mice.
    31. (2010). Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice.
    32. (1996). Energyubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids.
    33. (2000). Expression and functional consequences of 11β-hydroxysteroid dehydrogenase activity in human bone.
    34. (1995). gene expression during adipocyte differentiation.
    35. (2008). Genomic and nongenomic effects of glucocorticoids.
    36. (2011). Glucocorticoid-induced osteoporosis – a disorder of mesenchymal stromal cells?
    37. (2008). Glucocorticoid-inducedbonelossin mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization.
    38. (2006). Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient
    39. (2004). Glucocorticoids actdirectlyonosteoblastsandosteocytes to induce their apoptosis and reduceboneformationandstrength.
    40. (2006). Glucocorticoids promote chondrogenic differentiationof adulthumanmesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes.
    41. (1992). Glucocorticoids promote development of the osteoblast phenotype by selectively modulating expression of cell growth and differentiation associated genes.
    42. (2010). Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor.
    43. (2003). Growth retardation induced by dexamethasone is associated with increased apoptosis of the growth plate chondrocytes.
    44. (2006). Impaired cortical bone acquisition and osteoblast differentiation in mice with osteoblast-targeted disruption of glucocorticoid signaling.
    45. (1989). In vivo responsiveness to glucocorticoid correlated with glucocorticoid receptor content in peripheral blood leukocytes in normal humans.
    46. (1998). Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.
    47. (1997). Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis.
    48. (1993). Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men.
    49. (2008). Local and systemic glucocorticoid metabolism in inflammatory arthritis.Ann.
    50. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues.
    51. (1987). Mineralocorticoid activity of liquorice: 11β-hydroxysteroid dehydrogenase defi-ciency comes of age.
    52. (2001). Modulation of 11β-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation.
    53. (2008). Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss.
    54. (1999). Multilineage potential of adult human mesenchymal stem cells.
    55. (1988). Muscle and adipose tissue morphology and metabolism in Cushing’s syndrome.
    56. (2011). paper pending published: 03
    57. (2002). Pre-receptor regulation of glucocorticoid action by 11β-hydroxysteroid dehydrogenase: a novel determinant of cell proliferation.
    58. (2001). Regulation of expression of 11β-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.
    59. (1999). Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized,double-blind,placebocontrolled, parallel-group study.
    60. (2000). Risk of persistent growth impairment after alternateday prednisone treatment in children with cystic fibrosis.
    61. (2005). Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass.
    62. (1999). Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoidinducedosteoporosis.Endocrinology 140,
    63. (2010). Synergistic induction of local glucocorticoid generation by inflammatory cytokines and glucocorticoids: implications for inflammation associated bone loss.
    64. (2007). Teriparatide or alendronate in glucocorticoid-induced osteoporosis.
    65. (2010). The 11-betahydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy.
    66. (2010). The 11beta-hydroxysteroid dehydrogenase enzymes – arbiters of the effects of glucocorticoids in synovium and bone. Rheumatology (Oxford)
    67. (1932). The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism).
    68. (2009). The pituitary-adrenal axis and body composition.
    69. (2009). The role and regulation of 11betahydroxysteroid dehydrogenase type 1 in the inflammatory response.
    70. (2001). Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity.
    71. (2004). Transgenic expression of 11β-hydroxysteroid dehydrogenase type 2 in osteoblasts reveals an anabolic role for endogenous glucocorticoids in bone.
    72. (2001). Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized,doubleblind, placebo-controlled extension trial.
    73. (2000). Use of oral corticosteroids and risk of fractures.
    74. (2008). Variable expression of 11beta Hydroxysteroid dehydrogenase (11beta-HSD) isoforms in vascular endothelial cells.
    75. (2009). Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomisedcontrolledtrial.Lancet 373,

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.