Low-dose parathyroid hormone and estrogen reverse alkaline phosphatase activity suppressed by dexamethasone in mouse osteoblastic cells

Abstract

Glucocorticoid (GC)-induced osteoporosis (GIO) is frequently seen in patients with excessive GC. Numerous questions remain to be clarified about the pathogenesis and treatment of GIO, and the mechanism of GC-inhibited bone formation is not well known. Several studies suggest that parathyroid hormone (PTH) and hormone replacement therapy are effective for GIO. We therefore investigated whether PTH and estrogen would affect cell proliferation and alkaline phosphatase (ALP) activity inhibited by dexamethasone (Dex) in mouse osteoblastic cell-line MC3T3-E1 cells. Low-dose (10(-11) M) PTH as well as 10(-8) M 17-beta-estradiol (17beta-E2) significantly attenuated Dex-inhibited ALP activity, although 10(-8) M PTH did not affect it. ICI 182780 (10(-8) M) antagonized the effects of 17beta-E(2) on Dex-suppressed ALP activity. Neutralizing anti-IGF-I antibody (3 microg/ml) blocked the reverse effects of 17beta-E2 on ALP activity suppressed by Dex. PTH (10(-11) M), but not 17beta-E2, significantly attenuated [3H]thymidine incorporation inhibited by Dex. On the other hand, PTH and estrogen did not affect the level of 11-beta-hydrosteroid dehydrogenase type I mRNA increased by Dex. In conclusion, the present study demonstrated that low-dose PTH and estrogen reversed Dex-inhibited ALP activity in the mouse osteoblastic cell-line.

Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

“…Some studies have evaluated the effects of dexamethasone on osteoblastic or progenitor cell lines established from not only rodents but also humans. However, most of these studies aimed to clarify the mechanisms underlying steroid-induced osteoporosis [ 38 – 44 ]; furthermore, the cell lines evaluated were homogenous and the findings may thus be difficult to generalize to physiologically or clinically relevant cell populations. Dexamethasone has not been used for osteogenic induction in most cell lines, even though it has been shown that dexamethasone is required for osteogenic induction of heterogeneous bone marrow-derived cells and cells from other stromal tissues.…”

Anorexia nervosa and osteoporosis

“…The anti-resorptive effects of estrogen are mediated at least in part by (1) suppression of secretion of certain proinflammatory cytokines that stimulate osteoclast differentiation and action and prolong osteoclast survival, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and (2) an increase in secretion of transforming growth factor (TGF-)-β and osteoprotegerin (OPG), which suppress osteoclast activity and accelerate osteoclast apoptosis [24]. Estrogen may also inhibit osteoblast apoptosis [25,26]. In both genders, aromatization of androgens to estrogen accounts for decreased bone resorption, and testosterone also has direct anti-resorptive and bone anabolic effects [27].…”

Once-weekly teriparatide improves glucocorticoid-induced osteoporosis in patients with inadequate response to bisphosphonates

“…Glucocorticoids can suppress osteoblastic differentiation and activity, both of which many be overcome by PTH and bisphosphonates (Hayashi et al 2009 ). An in vitro study showed that low-dose PTH reversed glucocorticoid-inhibited alkaline phosphatase activity (Iu et al 2005 ). Intermittent PTH was found to prevent glucocorticoid-induced osteoblast and osteocyte apoptosis and preserve the rate of bone formation, BMD, and strength (Weinstein et al 2010 ).…”