scholarly journals Role of RANK ligand in mediating increased bone resorption in early postmenopausal women

2003 ◽  
Vol 111 (8) ◽  
pp. 1221-1230 ◽  
Author(s):  
Guitty Eghbali-Fatourechi ◽  
Sundeep Khosla ◽  
Arunik Sanyal ◽  
William J. Boyle ◽  
David L. Lacey ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Rank Ligand ◽  
Early Postmenopausal Women

scholarly journals Pivotal Role of OCL-Derived IGF1 in Drug Resistance and Bone Destruction in MM

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4336-4336
Author(s):  
Jumpei Teramachi ◽  
Kazuaki Miyagawa ◽  
Delgado-Calle Jesus ◽  
Jolene Windle ◽  
Noriyoshi Kurihara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Drug Resistance ◽  
Bone Resorption ◽  
Bone Marrow Cells ◽  
Critical Role ◽  
Bone Destruction ◽  
Bone Marrow Microenvironment ◽  
Rank Ligand ◽  
Marrow Cells

Multiple myeloma (MM) is largely incurable, and is characterized by devastating bone destruction caused by increased osteoclast (OCL) differentiation and bone resorption in more than 85% of MM patients. OCLs in MM not only promote bone resorption but also increase MM cell growth and drug resistance. Despite recent advances in anti-myeloma treatment, development of anti-MM drug resistance is a major limitation of MM therapy. Therefore, new treatment modalities are urgently needed to overcome drug resistance and decrease bone resorption. IGF1 is a crucial factor for tumor cell growth and survival of malignant cells, especially in MM. IGFI also contributes to development of drug resistance of MM cells to anti-MM agents, including proteasome inhibitors and immunomodulatory agents, but how OCLs contribute to drug resistance is still not clearly delineated. We found that IGF1 was highly expressed in OCLs attached to bone and bone marrow myeloid cells in vivo, and the expression levels of IGF1 in OCLs from MM bearing mice is higher than in normal OCLs. Intriguingly, OCLs produced more IGF1 (0.8 ng/ml/protein) than MM cells (not detected) and bone marrow stromal cells (BMSCs) (0.4 ng/ml/protein) in vitro. In addition, IGF1 protein expression in OCLs was upregulated (1.8 fold) by treatment with conditioned media (CM) from 5TGM1 murine MM cells, TNF-α or IL-6, major paracrine factors that are increased in the bone marrow microenvironment in MM. These results suggest that OCLs are a major source of local IGF1 in the MM bone marrow microenvironment. To further characterize the role of OCL-derived IGF1, we generated a novel mouse with targeted deletion of Igf1 in OCLs (IGF1-/--OCL), and assessed the role of OCL-derived IGF1 in drug resistance of MM cells and bone destruction. Treatment of 5TGM1 cells with bortezomib (BTZ) (3 nM, 48 hours) decreased the viability of 5TGM1 cells by 50%. Importantly, the cytotoxic effects of BTZ on MM cells were decreased (by 5%) when MM cells were cocultured with OCLs from wild type (WT) mice. In contrast, coculture of MM cells with IGF1-/--OCLs or WT-OCLs treated with IGF1 neutralizing antibody (IGF1-ab) did not block BTZ's effects on MM cell death. Consistent with these results, coculture of MM cells with IGF1-/--OCLs or WT-OCLs treated with IGF1-ab resulted in BTZ-induced caspase-dependent apoptosis in MM cells. We next examined the effects of OCLs on the signaling pathways responsible for MM cell survival. WT-OCL-CM promptly induced the phosphorylation of Akt and activation of p38, ERK and NF-κB in MM cells. However, these pathways were not activated by MM cells treated with IGF1-/--OCL-CM or IGF1-ab-treated WT-OCL-CM. Since adhesion of MM cells to BMSCs via interaction of VLA-4 and VCAM-1 plays a critical role in cell adhesion-mediated drug resistance (CAMDR) in MM, we tested if treatment of human BMSCs with human OCL-CM upregulated VCAM-1 expression. We found that OCL-CM upregulated VCAM-1 expression on BMSCs (x fold). In contrast, treatment of BMSCs with OCLs treated with IGF1-ab blocked VCAM-1 induction. These data suggest that OCL-derived IGF1 can contribute to MM cell drug resistance in the bone marrow microenvironment. We then examined the role of IGF1 inhibition on osteoclastogenesis and the bone resorption capacity of OCLs. RANK ligand induced the expression of cathepsin K and NFATc1 in CD11b+ bone marrow cells from WT mice, differentiation markers of OCLs, and the formation of TRAP-positive multinucleated OCLs. However, OCLs formed by RANK ligand treatment of CD11b+ bone marrow cells from IGF1-/- mice had markedly decreased cathepsin K and NFATc1 expression and OCL formation. Next, we tested the bone resorption capacity of OCLs formed by CD11b+ bone marrow cells from IGF1-/- mice vs. WT mice. Similar numbers of OCLs were cultured with RANK ligand on bone slices for 72 hours. The bone resorption activity of Igf1-/--OCLs was significantly decreased (70%) compared with WT-OCLs. These results suggest that OCL-derived IGF1 plays a critical role in MM drug resistance and bone destruction, and that inhibition of the effect of IGF1 in OCLs should decrease MM drug resistance and bone destruction. Disclosures Roodman: Amgen trial of Denosumab versus Zoledronate: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Calcium Supplementation Suppresses Bone Resorption in Early Postmenopausal Women

1998 ◽  
Vol 62 (1) ◽  
pp. 8-12 ◽  
Author(s):  
F. Scopacasa ◽  
M. Horowitz ◽  
J. M. Wishart ◽  
A. G. Need ◽  
H. A. Morris ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Calcium Supplementation ◽  
Early Postmenopausal Women

Role of serum FSH measurement on bone resorption in postmenopausal women

Endocrine ◽  
2011 ◽  
Vol 41 (2) ◽  
pp. 302-308 ◽  
Author(s):  
Antonia García-Martín ◽  
Rebeca Reyes-García ◽  
José Miguel García-Castro ◽  
Pedro Rozas-Moreno ◽  
Fernando Escobar-Jiménez ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women

scholarly journals Effect of Blockade of TNF-α and Interleukin-1 Action on Bone Resorption in Early Postmenopausal Women

2007 ◽  
Vol 22 (5) ◽  
pp. 724-729 ◽  
Author(s):  
Natthinee Charatcharoenwitthaya ◽  
Sundeep Khosla ◽  
Elizabeth J Atkinson ◽  
Louise K McCready ◽  
B Lawrence Riggs
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Interleukin 1 ◽  
Early Postmenopausal Women ◽  
Tnf Α

scholarly journals The Role of Parathyroid Hormone in Alveolar Bone Resorption on Postmenopausal Women

2020 ◽  
Vol 14 (1) ◽  
pp. 82-87
Author(s):  
Susi R. Puspitadewi ◽  
Lindawati S. Kusdhany ◽  
Sri Lelyati C. Masulili ◽  
Pitu Wulandari ◽  
Hanna B. Iskandar ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Postmenopausal Women ◽  
Alveolar Bone ◽  
Bone Mineralization ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Collection ◽  
Cross Sectional

Background: Postmenopausal women exhibit reduced bone mineralization, which causes bone resorption, including that of alveolar bone. Parathyroid hormone has been shown to play a role in alveolar bone resorption. Objective: This study aims to analyze relationships between parathyroid hormone and other factors that may contribute to alveolar bone resorption in postmenopausal women. Methods: This cross-sectional study included 82 postmenopausal women aged 50–74 years, who resided in Central and East Jakarta, Indonesia. Subjects' data were obtained through questionnaires, dental examinations, and blood collection for the examination of parathyroid hormone levels by enzyme-linked immunosorbent assay and using panoramic radiography to measure bone resorption. Results: Spearman correlation analysis showed a significant correlation between parathyroid hormone level (p = 0.005) and extent of alveolar bone resorption, but age (p = 0.292), menopausal duration (p = 0.244), and number of missing teeth (p = 0.517) were not significantly correlated with the extent of alveolar bone resorption. Conclusion: Various factors play a role in the mechanism of bone resorption, so knowing the role of each factor is expected to reduce the effects of alveolar bone resorption that occurs in postmenopause. Among the factors investigated in this study, the parathyroid hormone was the sole factor correlated with postmenopausal alveolar bone resorption.

β-blockers reduce bone resorption marker in early postmenopausal women

2005 ◽  
Vol 32 (6) ◽  
pp. 738-745 ◽  
Author(s):  
Julie A. Pasco ◽  
Margaret J. Henry ◽  
Geoffrey C. Nicholson ◽  
Hans G. Schneider ◽  
Mark A. Kotowicz
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Bone Resorption Marker ◽  
Early Postmenopausal Women ◽  
Β Blockers

Role of Low Levels of Endogenous Estrogen in Regulation of Bone Resorption in Late Postmenopausal Women

2002 ◽  
Vol 17 (1) ◽  
pp. 172-178 ◽  
Author(s):  
Hassan M. Heshmati ◽  
Sundeep Khosla ◽  
Simon P. Robins ◽  
W. Michael O'Fallon ◽  
L. Joseph Melton ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Endogenous Estrogen ◽  
Low Levels

Inhibition of Bone Resorption by Divided-Dose Calcium Supplementation in Early Postmenopausal Women

2000 ◽  
Vol 67 (6) ◽  
pp. 440-442 ◽  
Author(s):  
F. Scopacasa ◽  
A. G. Need ◽  
M. Horowitz ◽  
J. M. Wishart ◽  
H. A. Morris ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Divided Dose ◽  
Calcium Supplementation ◽  
Early Postmenopausal Women
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