RESUMEN
BACKGROUND: Osteoblasts possess strong growth modulatory activity on haematopoietic stem cells and progenitors. We sought to characterise the growth and differentiation modulatory activities of human osteoblasts at distinct stages of maturation on cord blood (CB) progenitors in the context of osteoblast conditioned medium (OCM). METHODS: OCM was produced from MSC-derived osteoblasts (M-OST) at distinct stages of maturation. The growth modulatory activities of the OCM were tested on CB CD34+ cells using different functional assays. RESULTS: OCMs raised the growth of CB cells and expansion of CD34+ cells independently of the maturation status of M-OST. However, productions of immature CB cells including committed and multipotent progenitors were superior with OCM produced with immature osteoblasts. Osteogenic differentiation was accompanied by the upregulation of IGFBP-2, by several members of the Angpt-L family of growth factor, and by the Notch ligands Dll-1 and Dll-4. However, the growth activity of OCM and the in vivo engraftment properties of OCM-expanded CB cells were retained after IGFBP-2 neutralisation. Similarly, OCM-mediated expansion of CB myeloid progenitors was largely independent of Notch signalling. CONCLUSIONS: These results demonstrate that immature osteoblasts possess greater regulatory activity over haematopoietic progenitors, and that this activity is not entirely dependent on Notch signalling.
Asunto(s)
Diferenciación Celular/genética , Sangre Fetal/metabolismo , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/metabolismo , Osteoblastos/metabolismo , Comunicación Paracrina/genética , Proteínas Adaptadoras Transductoras de Señales , Proteína 1 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/genética , Proteínas Similares a la Angiopoyetina/metabolismo , Animales , Antígenos CD34/genética , Antígenos CD34/metabolismo , Proteínas de Unión al Calcio , Medios de Cultivo Condicionados/farmacología , Sangre Fetal/citología , Sangre Fetal/efectos de los fármacos , Regulación de la Expresión Génica , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos NOD , Osteoblastos/citología , Cultivo Primario de Células , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal , Trasplante Heterólogo , Irradiación Corporal TotalRESUMEN
Objective: Puberty has a significant contribution to the final height. Therefore, it is crucial to understand the normal variations in the onset and tempo of puberty in a specific population. In this study, we aimed to provide normative data on the timing of puberty and late pubertal height (LPH) in Saudi schoolboys in Riyadh. Methods: This is a cross-sectional field study (2011-2013) including Saudi schoolboys (grades 1-12; aged 6 to 19 years). Schools were chosen to represent the population from urban and rural areas in the Riyadh region. Pubertal maturity staging for gonads was assessed by measuring testicular size using a Prader orchidometer and assessing the Tanner staging of pubic hair. The marginal mean age was calculated using regression analysis. Results: We recruited 1086 schoolboys. The estimated mean age of pubertal onset at G2 was 11.8 (95% CI 11.60-12.0) years, for gonadal development at G3 was 13.2 (95% CI 12.9-13.5), G4 = 15.0 (95% CI 14.7-15.2), and G5 = 16.1 (95% CI 15.9-16.3) years, and for pubic hair stage 2 (PH2) was 12.6 (95% CI 12.4-12.9) years. The estimated time from G2/PH2 to G5/PH5 was 4.3 and 3.9 years, respectively. At the onset of puberty, the mean height was 144.7 cm and it reached 167.8 cm at G5 with a pubertal height gain of 23.1 cm. Conclusion: Our data present the norms of the timing of puberty and LPH in Saudi schoolboys. Saudi adolescent males are shorter than some European and American comparatives mainly due to shortness during childhood. However, they could have shorter LPH than Turkish, Greek, Thai, and Japanese due to a less pubertal height gain.