Differential effects of glucocorticoids on bone resorption in neonatal mouse calvariae stimulated by peptide and steroid-like hormones

Conaway, H. Herschel; Grigorie, Daniel; Lerner, Ulf H.

doi:10.1677/joe.0.1550513

Cited by 31 publications

(23 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bones were then extensively washed and subsequently cultured submerged in 24-wells containing 1 ml of medium in the absence of all-trans-retinoic acid (ATRA) or test substances (controls) or in the presence of ATRA (10 -7 M) with or without test substances. ATRA was used to induce osteoclastic bone resorption in the calvariae (15). The release of 45 Ca induced by ATRA in this bioassay is associated with enhanced release of also type I collagen and is inhibited by calcitonin which demonstrates that 45 Ca release is a useful parameter of osteoclastic bone resorption (data not shown).…”

Section: Fluorimetric Cytotoxicity Assay (Fmca)mentioning

confidence: 80%

Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis

Holmberg¹

2010

Int J Oncol

View full text Add to dashboard Cite

Abstract. Advanced stage prostate and breast cancer frequently metastasize to the skeleton (~75%). An additional complication in these patients, that further affects the bones, is that their hormonal treatment, induces osteoporosis. Bisphosphonates (bpns) are standard drugs against osteoporosis and have been shown to have clinically significant anti-tumor effects. This study describes the development of a new polybisphosphonate conjugate (ODX) with enhanced dual efficacy i.e. with anti-bone resorption and anti-tumor properties. Zoledronic acid (Zometa ® ) was used as a positive control (at equimolar concentrations). Alendronic acid and aminoguanidine were conjugated to oxidized dextran with subsequent reductive amination (on average ~8 alendronate and ~50 guanidine moieties per conjugate). ODX was tested in a bone resorption assay for its capacity to inhibit bone resorbing osteoclasts (bone organ culture from neonatal mice, 45 Ca labelled bone mineral). Tumor cell toxicity was studied on prostate (PC3) and breast cancer (MDA231, MDA453) cell cultures. Two methods were employed, a fluorescent cytotoxicity assay (FMCA) and an apoptosis assay (Annexin V assay). In the bone resorption assay, Zometa and ODX showed very similar potency with 50% osteoclast inhibition at ~20 nM and 100% at 0.2 μM. In the FMCA, IC 50 for ODX was at ~2 μM and 25 μM for Zometa (PC3). In the apoptosis assay, ODX induced ~85-97% apoptosis at 10 μM in both cell lines, while Zometa failed to induce any significant apoptosis in any of the cell lines at the tested concentration range (10 nM-10 μM). ODX appears to be a promising drug candidate with high dual efficacy for the treatment of bone metastasis and osteoporosis. It has both potent osteoclast inhibiting properties and enhanced anti-tumor efficacy.

show abstract

Section: Fluorimetric Cytotoxicity Assay (Fmca)mentioning

confidence: 80%

Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis

Holmberg¹

2010

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Only recently, transgenic mouse technology has allowed the generation of two osteoclastic cell lines [68] . Early in vitro studies on isolated osteoclasts and bone organ cultures suggested that GCs may inhibit bone resorption [69,70] , whereas more recent studies indicate that GCs may rather stimulate bone resorption [71][72][73] . The mechanisms by which GCs regulate osteoclast formation and activation are unclear.…”

Section: Effects Of Gcs On Osteoclast Activitymentioning

confidence: 99%

Glucocorticoid-Induced Osteoporosis: From Basic Mechanisms to Clinical Aspects

Alesci

Martino

Ilias

et al. 2005

Neuroimmunomodulation

View full text Add to dashboard Cite

Glucocorticoid (GC)-induced osteoporosis (GCOP) is the most common cause of osteoporosis in adults aged 20–45 years as well as the most common cause of iatrogenic osteoporosis. GC excess, either endogenous or exogenous, induces bone loss in 30–50% of cases. Indeed, bone loss leading to fractures is perhaps the most incapacitating, sometimes partially irreversible, complication of GC therapy. Nevertheless, GCOP is often underdiagnosed and left untreated. The following article provides an update on the cellular and molecular mechanisms implicated in the pathophysiology of GC-induced bone loss, as well as some guidelines on diagnostic, preventive and therapeutic strategies for this medical condition, in an effort to promote a better knowledge and greater awareness of GCOP by both the patient and the physician.

show abstract

“…A negative influence of retinoids on skeletal integrity has also been reported in various animal studies, most of them demonstrating that increased periostal bone resorption is an underlying cause [7,[37][38][39]. Since similar observations were made in organ cultures, it was hypothesized that osteoclasts are the main cells responsible for the effects of retinoids on bone [40][41][42][43][44]. Importantly, however, experiments with cultured osteoclasts did not confirm such a direct influence, since it was found that retinoids had a negative effect on their differentiation and resorptive activity [5][6][7].…”

Section: Discussionmentioning

confidence: 68%

Immediate effects of retinoic acid on gene expression in primary murine osteoblasts

et al. 2015

View full text Add to dashboard Cite

Consistent with clinical observations demonstrating that hypervitaminosis A is associated with increased skeletal fracture risk, we have previously found that dietary retinol deprivation partially corrects the bone mineralization defects in a mouse model of X-linked hypophosphatemic rickets. That retinol-dependent signaling pathways impact the skeleton is further supported by various findings demonstrating a negative influence of retinoic acid (RA) on bone-forming osteoblasts. We hypothesized that RA would directly regulate the expression of specific target genes in osteoblasts, and we aimed to identify these by genome-wide expression analyses. Here we show that high dietary retinol intake in mice causes low bone mass associated with increased osteoclastogenesis and decreased osteoblastogenesis, but intact bone matrix mineralization. We additionally found that short-term treatment of primary osteoblasts with RA causes a rapid induction of specific genes involved in either retinol-dependent signaling (i.e. Rara, Crabp2) or skeletal remodeling (i.e. Twist2, Tnfsf11). In contrast, neither expression of established osteoblast differentiation markers nor the proliferation rate was immediately affected by RA administration. Collectively, our data suggest that the negative effects of vitamin A on skeletal integrity are explainable by an immediate influence of RA signaling on specific genes in osteoblasts that in turn influence bone remodeling.

show abstract

Differential effects of glucocorticoids on bone resorption in neonatal mouse calvariae stimulated by peptide and steroid-like hormones

Cited by 31 publications

References 29 publications

Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis

Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis

Glucocorticoid-Induced Osteoporosis: From Basic Mechanisms to Clinical Aspects

Immediate effects of retinoic acid on gene expression in primary murine osteoblasts

Contact Info

Product

Resources

About