Glucocorticoid-induced autophagy in osteocytes

Abstract

Glucocorticoid (GC) therapy is the most frequent cause of secondary osteoporosis. In this study we have demonstrated that GC treatment induced the development of autophagy, preserving osteocyte viability. GC treatment resulted in an increase in autophagy markers and the accumulation of autophagosome vacuoles in vitro and in vivo promoted the onset of the osteocyte autophagy, as determined by expression of autophagy markers in an animal model of GC-induced osteoporosis. An autophagy inhibitor reversed the protective effects of GCs. The effects of GCs on osteocytes were in contrast to tumor necrosis factor α (TNF-α), which induced apoptosis but not autophagy. Together this study reveals a novel mechanism for the effect of GC on osteocytes, shedding new insight into mechanisms responsible for bone loss in patients receiving GC therapy. © 2010 American Society for Bone and Mineral Research.

Suppression of Autophagy in Osteocytes Mimics Skeletal Aging

“…The results of the present study suggest that a decline in osteocyte autophagy may also contribute to the adverse effects of age on the skeleton. Recent studies have provided evidence that glucocorticoids stimulate autophagy in the MLO-Y4 osteocytic cell line (51). Based on these studies, the increased endogenous glucocorticoid levels in aged mice might be expected to increase autophagy.…”

Osteoporosis and autophagy: What is the relationship?

“…61 Low-dose glucocorticoid treatment has also been shown to induce autophagy in osteocytes in response to increased oxidative stress caused by treatment, preserving the viability of these cells. [62][63][64] Studies indicate that autophagy also plays an important role in bone resorption by osteoclasts. 65 It has been reported that proteins involved in the autophagic pathway are important in the regulation of osteoclastogenesis, 66,67 indicating that this process participates both in bone formation and resorption.…”

Dexamethasone reduces ATDC5 chondrocyte cell viability by inducing autophagy

“…Administration of GCs leads to a reduction in bone mineral density (BMD), decreased generation of osteoblasts and osteocytes and prolonged lifespan of osteoclasts, with fractures occurring in 30-50% of patients chronically treated with GCs (1). Recent studies have demonstrated that GCs can induce apoptosis and autophagy in osteocytes (4)(5)(6). The influence of GCs has been rarely reported on chondrocytes, which play a key role in skeletal development.…”