title: 17β-estradiol differently affects osteogenic differentiation of mesenchymal stem/stromal cells from adipose tissue and bone marrow.
abstract: Adipose-derived and bone marrow stem/stromal cells (ASCs and BMSCs) have been often compared for their application in regenerative medicine, and several factors sustaining their differentiation and efficacy have been investigated. 17 β-estradiol (E2) has been reported to influence some functions of progenitor cells. Here we studied the effects of 10 and 100nM E2 on ASC and BMSC vitality, proliferation and differentiation towards osteogenic and adipogenic lineages. E2 did not modulate ASC and BMSC vitality and growth rate, while the hormone produced a pro-adipogenic effect on both mesenchymal stem/stromal cells (MSCs). In particular, the synergy between 7-day pre-treatment and 100nM E2 led to the most evident result, increasing lipid vacuoles formation in ASCs and BMSCs of +44% and +82%, respectively. Despite the fact that E2 did not alter collagen deposition of osteo-induced MSCs, we observed a different modulation of ASC and BMSC alkaline phosphatase (ALP) activity. Indeed, this osteogenic marker was always enhanced by 17 β-estradiol in BMSCs, and 7-day pre-treatment with 100nM E2 increased it of about 70%. In contrast, E2 weakened ASC osteogenic potential, reducing their ALP activity of about 20%, with the most evident effect on ASCs isolated from pre-menopausal women (-30%). Finally, we identified an estrogen receptor α (ERα) variant of about 37kDa expressed in both MSCs. Interestingly, adipogenic stimuli drastically reduced its expression, while osteogenic ones mildly increased this isoform in BMSCs only. In conclusion, E2 positively affected the adipogenic process of both MSCs while it favored osteogenic induction in BMSCs only, and both mesenchymal progenitors expressed a novel 37kDa ER-α variant whose expression was modulated during differentiation.
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy; IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy. Electronic address: stefania.niada@unimi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Niada
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy; IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy. Electronic address: chiara.giannasi@unimi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Giannasi
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy; IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy. Electronic address: lorena.ferreira@unimi.it.
authors.forename: Lorena Maria Josè
authors.initials: LM
authors.lastname: Ferreira
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy; IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy. Electronic address: anna.milani@unimi.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Milani
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy; IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy. Electronic address: elena.arrigoni@hotmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Arrigoni
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milan, Italy; IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy. Electronic address: anna.brini@unimi.it.
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Brini
mesh_terms: D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D004958:Estradiol / Q000008:administration & dosage; D047628:Estrogen Receptor alpha / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D044968:Regenerative Medicine
chemical_list: D047628:Estrogen Receptor alpha; D004958:Estradiol
keywords: 17 β-estradiol; Adipogenic differentiation; Estrogen receptor α; Mesenchymal stem/stromal cells; Osteogenic differentiation