title: Rivaroxaban, a direct inhibitor of the coagulation factor Xa interferes with hormonal-induced physiological modulations in human female osteoblastic cell line SaSO2.
abstract: The use of anticoagulants has been associated with systemic osteoporosis and increased risk for poor fracture healing but is inevitable following major orthopedic surgery of lower limbs. Rivaroxaban A (R) is an anticoagulant recently introduced in the clinical setting, which is a specific factor Xa inhibitor. We reported previously that R significantly inhibited cell growth, energy metabolism and alkaline phosphatase activity in human osteoblastic cell line SaOS2, with no effect on mineralization, indicating transient inhibition of bone formation. We now investigated the effects of R on SaOS2 response to osteoblast-modulating hormones. At sub-confluence cells were treated with: estradiol-17β (E2), the phytoestrogens daidzein (D) and biochainin A (BA), the carboxy-pytoestrogenic derivative carboxy-D (cD), the estrogen receptor α (ERα) agonist PPT, the estrogen receptor β (ERβ) agonist DPN, parathyroid hormone (PTH) and several vitamin D metabolites and analogs with/without R for 24h. All hormones tested stimulated significantly DNA synthesis (DNA), creatine kinase (CK) and alkaline phosphatase (ALP) specific activities, but all these stimulations were totally inhibited when given together with R. R had no effect on mRNA expression of ERα, ERβ and 25 Hydroxy-vitamin D3-1α hydroxylase (1OHase), but inhibited hormonal modulations of mRNA expressions. In conclusion R inhibited significantly hormonal stimulation of different parameters indicating inhibition of not only the early stages of bone formation, but also the stimulatory effects of bone modulating hormones with a yet unclear mechanism. The relevance of these findings to human bone physiology is yet to be investigated.
authors: Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel. dalias@tasmc.health.gov.il
authors: Dalia
authors: D
authors: Somjen
authors: Sara
authors: S
authors: Katzburg
authors: Roi
authors: R
authors: Gigi
authors: Oleg
authors: O
authors: Dolkart
authors: Orli
authors: O
authors: Sharon
authors: Moshe
authors: M
authors: Salai
authors: Naftali
authors: N
authors: Stern
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000925:Anticoagulants / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D019833:Genistein / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000069552:Rivaroxaban; D012502:Sapogenins / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology; D011422:Propionates
chemical_list: D000469:Alkaline Phosphatase; D000925:Anticoagulants; D003402:Creatine Kinase; D004247:DNA; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015951:Factor Xa; D065427:Factor Xa Inhibitors; D019833:Genistein; D036145:Ginsenosides; D007529:Isoflavones; D009025:Morpholines; D009570:Nitriles; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D000069552:Rivaroxaban; D012502:Sapogenins; D013876:Thiophenes; D014807:Vitamin D; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C506487:ESR1 protein, human; C507965:ginsenoside 20S-protopanaxatriol; C004742:daidzein; C004541:biochanin A