RESUMO
OBJECTIVES: Preterm infants are born with low bone mineral. Neonatal stress further impedes bone mineralization. Clinical evidence suggests that tactile and kinesthetic stimulation (TKS) improves bone phenotype and decreases stress response. Clinical and translational studies indicate the IGF-1 axis, responsible for postnatal growth and bone mineralization, is a key player. We hypothesized that TKS would attenuate the negative impact of neonatal stress on bone phenotype and the IGF-1 axis in weanling rats. METHODS: Neonatal stress (STRESS) or TKS (STRESS + 10min TKS) was administered from D6 to D10. Control animals received standard care. Tissue was harvested on D21. Dual energy x-ray absorptiometry (DXA) and bone morphometry were performed and serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF-1, IGF-1 receptor (IGF-1R), and growth hormone receptor (GHR) were measured. RESULTS: Neonatal stress increased bone mineral content (BMC), area (BA), growth plate width, liver IGF-1 mRNA, and serum IGF-1. TKS maintained areal bone mineral density (aBMD) and bone specific IGF-1 and IGF-1R mRNA while STRESS decreased compared to controls. CONCLUSIONS: Neonatal stress results in apparent accelerated growth response. TKS differed from STRESS with improved tibia aBMD and increased bone specific IGF-1 mRNA.
Assuntos
Desenvolvimento Ósseo/fisiologia , Osso e Ossos/fisiologia , Cinestesia/fisiologia , Estresse Psicológico/fisiopatologia , Tato/fisiologia , Absorciometria de Fóton , Animais , Animais Recém-Nascidos , Biomarcadores , Peso Corporal/fisiologia , Reabsorção Óssea/patologia , Osso e Ossos/anatomia & histologia , Calcificação Fisiológica/fisiologia , Densitometria , Epífises/anatomia & histologia , Epífises/crescimento & desenvolvimento , Epífises/fisiologia , Feminino , Lâmina de Crescimento/anatomia & histologia , Lâmina de Crescimento/fisiologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Gravidez , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Tíbia/anatomia & histologia , Tíbia/crescimento & desenvolvimento , Tíbia/fisiologiaRESUMO
OBJECTIVES: Neonatal stress impairs postnatal bone mineralization. Evidence suggests that mechanical tactile stimulation (MTS) in early life decreases stress hormones and improves bone mineralization. Insulin-like growth factor (IGF1) is impacted by stress and essential to bone development. We hypothesized that MTS administered during neonatal stress would improve bone phenotype in later life. We also predicted an increase in bone specific mRNA expression of IGF1 related pathways. METHODS: Neonatal stress (STRESS) and MTS (STRESS+10 min of MTS) were given from D6 to D10 of rat life and tissue was harvested on D60 of life. Dual energy x-ray absorptiometry (DXA), bone morphometry, serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF1, IGF1 receptor (IGF1R), and growth hormone receptor (GHR) were measured. RESULTS: Stress resulted in reduced bone area and bone mineral content (BMC) compared to naive control (CTL). MTS intervention increased BMC and tibial growth plate width compared to STRESS. MTS also resulted in higher osteocalcin, and, in males, lower TRAP (p<0.05). MTS resulted in three-fold, two-fold, and six-fold higher bone specific IGF1, IGF1R, and GHR, respectively (p ≤ 0.001) compared to STRESS. CONCLUSIONS: MTS in early postnatal life improves long-term bone mineralization. IGF1 and related pathways may explain improved BMC.
