Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy

Abstract

Cartilage and bone are severely affected by glucocorticoids (GCs), steroid hormones that are frequently used to treat inflammatory diseases. Major complications associated with long-term steroid therapy include impairment of cartilaginous bone growth and GC-induced osteoporosis. Particularly in arthritis, GC application can increase joint and bone damage. Contrarily, endogenous GC release supports cartilage and bone integrity. In the last decade, substantial progress in the understanding of the molecular mechanisms of GC action has been gained through genome-wide binding studies of the GC receptor. These genomic approaches have revolutionized our understanding of gene regulation by ligand-induced transcription factors in general. Furthermore, specific inactivation of GC signaling and the GC receptor in bone and cartilage cells of rodent models has enabled the cell-specific effects of GCs in normal tissue homeostasis, inflammatory bone diseases, and GC-induced osteoporosis to be dissected. In this review, we summarize the current view of GC action in cartilage and bone. We further discuss future research directions in the context of new concepts for optimized steroid therapies with less detrimental effects on bone.

Молекулярно-Клітинні Механізми Захисної Дії Вітаміну D3 При Експериментальному Преднізолон-Індукованому Остеопорозі

“…Однак відомо, що пацієнти, які тривалий час приймають пероральні стероїдні протизапальні препарати, мають підвищений ризик розвитку остео-порозу зі значними втратами кісткової маси в перші місяці лікування [4,5]. Стероїдний остеопороз нале-жить до класу вторинних остеопорозів, що виклика-ється як патологічним підвищенням ендогенної про-дукції глюкокортикоїдів наднирниками, так і може бути результатом тривалого введення синтетичних Оригінальні дослідження / Original Researches аналогів кортикостероїдів, що застосовуються для лікування численних захворювань людини.…”

Prednisolone and vitamin D(3) modulate oxidative metabolism and cell death pathways in blood and bone marrow mononuclear cells

“…Osteoporosis is among the most devastating side effects of chronic GC administration associated with significant alterations of mineral metabolism and bone formation [1]. Glucocorticoidinduced osteoporosis causes an increase in bone fractures, delays healing of fractures, and affects the quality of life.…”

“…The underlying mechanism of osteoporosis is associated with the prevalence of osteoclast-dependent bone resorption over its osteoblast-mediated formation and mineralization leading to loss of bone mass and mineral density [1]. GCs modify osteoblastic and osteoclastic cell differentiation, number, and function either directly or via influencing the recruitment of their precursors from the bone marrow [2].…”

Animal models to explore the effects of glucocorticoids on skeletal growth and structure

“…The relative efficacy and potency of GC may also depend on the system studied, for example the potency for effects on bone metabolism may be quite different to those on glucose and fat metabolism , Wallace et al 2003. In addition, it is not yet clear whether genomic or non-genomic pathways play the major role in GIO (Hartmann et al 2016). Altered bone structure was observed in two-month-old male mice treated with 15 mg/kg/day of corticosterone (Herrmann et al 2009), but only 2.8 mg/kg/day of methylprednisolone was needed to induce similar changes in mice of same age and sex (Yao et al 2016).…”