Atorvastatin Reduces Circulating Osteoprogenitor Cells and T‐Cell RANKL Expression in Osteoporotic Women: Implications for the Bone–Vascular Axis. Issue 1 (February 2016)

• Record Type: Journal Article
• Authors: Rattazzi, Marcello; Faggin, Elisabetta; Buso, Roberta; Di Virgilio, Roberto; Puato, Massimo; Plebani, Mario; Zaninotto, Martina; Palmosi, Tiziana; Bertacco, Elisa; Fadini, Gian Paolo; Pauletto, Paolo
• Is Part Of: Cardiovascular therapeutics. Volume 34:Issue 1(2016:Feb.)
• Page Start: 13
• Page End: 20
• Publication Date: 2016-02
• Subjects: Atorvastatin -- Osteoporosis -- Osteoprogenitors -- RANKL -- T cells; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular system -- Diseases -- Chemotherapy -- Periodicals; Cardiovascular Agents -- Periodicals; Cardiovascular Diseases -- drug therapy -- Periodicals; Agents cardiovasculaires -- Périodiques; Appareil cardiovasculaire -- Maladies -- Chimiothérapie -- Périodiques; 616.1005
• DOI: 10.1111/1755-5922.12163
• Languages: English
• ISSNs: 1755-5914

Abstract

Summary: Aim: Circulating osteoprogenitors and receptor activator of nuclear factor kappa‐B ligand (RANKL) expression in immune cells have been implicated in the pathogenesis of osteoporosis and vascular calcification. The role played by statin therapy in the bone–vascular axis is unknown. Methods: Twenty naïve postmenopausal osteoporotic hypercholesterolemic women were treated with Atorvastatin 40 mg/day for 3 months. Gene expression analysis was performed to assess modification in osteoprotegerin (OPG)/RANK/RANKL expression in isolated T cells and monocytes. A flow cytometry analysis was used to study changes in the levels of circulating osteoprogenitor cells. Results: After 3 months of treatment, Atorvastatin significantly reduced total cholesterol and LDL‐C, without affecting HDL‐C and triglycerides. Among circulating bone and phosphocalcium homeostasis markers, we found a significant increase in OPG levels ( P < 0.01) and a modest reduction in osteocalcin (OCN) ( P < 0.05). We also observed a significant reduction in RANKL expression in T cells ( P < 0.05). No differences were found in the expression of RANK in T cells and RANKL and RANK in monocytes. OPG expression was low in both immune cell types and was not affected by the treatment. As for circulating osteoprogenitors, we found a significant reduction of CD34 + BAP + ( P < 0.05) and CD34 + OCN + BAP + ( P < 0.05) cells. In vitro studies showed that Atorvastatin reduced RANKL expression in activated human T‐lymphoblastoid cells (Jurkat cell line). Conclusions: Three‐month Atorvastatin treatment leads to a reduction in circulating osteoprogenitor cells and RANKL expression in T cells, as well as increase in OPG serum levels. These data suggest that statins could have protective effects in the bone–vascular axis.