title: Inhibition of the osteogenic differentiation of mesenchymal stem cells derived from the offspring of rats treated with caffeine during pregnancy and lactation.
abstract: Caffeine is an alkaloid that is widely consumed due to its presence in drugs, coffee, tea, and chocolate. This compound passes to offspring through the placenta and milk; can cause teratogenic mutations; and reduces the formation, growth, and mass of bone. Because mesenchymal stem cells (MSCs) are responsible for generating the entire skeleton, we hypothesized that these cells are targets of caffeine. This study evaluated the osteogenic differentiation of MSCs derived from the offspring of rats treated with caffeine during pregnancy and lactation. Twenty-four adult Wistar rats were randomly divided into four groups, including one control group and three experimental groups treated with 25, 50, or 100 mg/kg of caffeine. At weaning, three 21-day-old pups from each dam in each group were euthanized for extraction of bone marrow cells for in vitro tests. Caffeine doses of 50 and 100 mg/kg significantly reduced the activity of alkaline phosphatase at 7, 14, and 21 days and the expression of collagen I at 21 days. However, the expression of gene transcripts for alkaline phosphatase, Runx-2, and bone sialoprotein, as well as the synthesis of mineralization nodules, decreased significantly in all groups treated with caffeine. The expression of osteocalcin was significantly reduced only in the group treated with 50 mg/kg caffeine. The caffeine that passes from the mother to the offspring during pregnancy and lactation reduces the osteogenic differentiation of MSCs. We propose that this reduction in the osteogenic potential of MSCs may be involved in the pathogenesis of osteopenia resulting from caffeine consumption.
authors.affiliation: a Núcleo de Células Tronco e Terapia Celular Animal (NCT-TCA) do Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária , Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Amanda Maria Sena
authors.initials: AM
authors.lastname: Reis
authors.affiliation: a Núcleo de Células Tronco e Terapia Celular Animal (NCT-TCA) do Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária , Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Natália de Melo
authors.initials: Nde M
authors.lastname: Ocarino
authors.affiliation: a Núcleo de Células Tronco e Terapia Celular Animal (NCT-TCA) do Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária , Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Jankerle Neves
authors.initials: JN
authors.lastname: Boeloni
authors.affiliation: b Laboratório de Imunologia Celular e Biologia Molecular do Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: b Laboratório de Imunologia Celular e Biologia Molecular do Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Alfredo Miranda
authors.initials: AM
authors.lastname: Goes
authors.affiliation: b Laboratório de Imunologia Celular e Biologia Molecular do Departamento de Bioquímica e Imunologia , Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Andrea da Fonseca
authors.initials: Ada F
authors.lastname: Ferreira
authors.affiliation: a Núcleo de Células Tronco e Terapia Celular Animal (NCT-TCA) do Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária , Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais , Brazil.
authors.forename: Rogéria
authors.initials: R
authors.lastname: Serakides
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D007774:Lactation / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010641:Phenotype; D011247:Pregnancy; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D002110:Caffeine; D000469:Alkaline Phosphatase
keywords: Caffeine; lactation; pregnancy; rat; stem cell