Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Multiple myeloma is a haematologic malignancy that is characterized by osteolytic bone lesions, wherein coupled bone remodeling is disrupted with increased osteoclast activation and decreased osteoblast differentiation. In this study, we examined the effect of adenosine on osteoblast and osteoclast differentiation derived from multiple myeloma (MM) patients.
Methods:
Human bone marrow was collected from multiple myeloma patients. Bone marrow stromal cells (BMSCs) and bone marrow derived mononuclear (BMMs) cells were isolated and osteoblasts and osteoclasts were cultured, respectively. Adenosine A1 receptor agonist CHA and antagonist Rolofylline, A2a receptor agonist CGS and antagonist ZM, and A2b receptor agonist BAY and antagonist MRS 1754, A3 receptor agonist IB-MECA and antagonist MRS 1191; and dipyridamole, a nucleoside transport inhibitor, were added to the culture media. Alkaline phosphatase (ALP) activity assay was used to quantitate the osteoblast differentiation. In vitro osteoblast calcification was determined by alizarin red staining. TRAP+ staining was used to examine the osteoclast differentiation and bone resorption assay was used to study the osteoclast activity.
Results:
We found that A1R blockade by rolofylline and A2aR ligation by CGS21680 inhibited differentiation of both normal and MM BMMs into TRAP+ multinucleated cells (IC50= 1nM for A1R, IC50= 10μM for A2aR; p<0.001, n=3 for both). The A2A receptor antagonist completely reversed the effects of CGS21680 on osteoclast differentiation. Moreover, enhanced adenosine accumulation in the presence of dipyridamole (0.5μM) and A2bR activation promoted the differentiation of BMSCs into osteoblasts shown by Arlizarin red staining and ALP activity assay (by 1.8 ± 0.41 and 1.57 ± 0.26 fold, respectively, p<0.05, compared with osteogenic media only, n=3 for both).
Conclusion: These results indicate that adenosine receptors may be useful targets for the treatment and prevention of MM-induced bone disease.
Disclosure:
W. He,
None;
A. Mazumder,
None;
B. N. Cronstein,
Canfite BioPharma,
1,
NIH, URL Pharma, OSI,
2,
Bristol-Myers Squibb, Novartis, URL, Regeneron, Gismo Therapeutics,
5,
Arthritis Foundation, SLE Foundation,
6,
Patents on use of adenosine receptor antagonists to treat or prevent fibrosis. Multiple other patents.,
.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adenosine-regulates-bone-metabolism-via-a1-a2a-and-a2b-receptors-in-bone-marrow-cells-from-normal-and-patients-with-multiple-myeloma/