Contributions
Abstract: EP1438
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Background: Neural stem cells (NSCs) differentiation into functional neurons and oligodendrocytes are insufficient in MS. Bone morphogenic proteins (BMPs) are known to regulate NSCs differentiation and antagonizing BMPs is required for neurons and oligodendrocytes differentiation.
Methods: Sixty six untreated RR-MS patients and 44 matched HC or control cerebrospinal fluid (CSF) donors were included in the study. The levels of BMP-2,-4 &5 and their antagonists, noggin and follistatin were measured in the sera and CSF by ELISA. P19 cells serve as neuronal stem cells (NSC) model, they acquire MAP-2+ neuronal phenotype in response to retinoic acid (RA). Correlation between BMPs, noggin and follistatin was calculated by spearman´s p-value using the Bonferroni´s correction. The effect of sera from RR-MS patients or HC on P19 cells phenotype was examined by stimulating P19 cells with RA, for 4 days and incubation with or without BMP2 neutralizing Ab. MAP-2 expression was examined by immunofluorescence staining and confocal microscopy on day 8.
Results: BMPs, noggin and follistatin, were detected only in the sera but not in the CSF. BMP-2 was significantly higher in sera of RR-MS patients (130.6 ± 47.9 pg/ml) vs. HC (15.6 ± 6.3 pg/ml, p= 0.020). No significant differences between RR-MS patients and HC were found for the other BMPs, or their antagonists. A positive correlation was found between all 3 BMPs only in the RR-MS group (BMP-2 vs. BMP-4, r= 0.52, p= 0.0002; BMP-2 vs. BMP-5, r= 0.52, p= 0.0003; BMP-4 vs. BMP-5, r= 0.61,
p= 0.0001). A positive correlation was found between follistatin and noggin only in HC group (r= 0.61,
p= 0.0035). BMP-2 inhibited the RA-mediated MAP-2 expression on P19 cells. In the presence of RA and BMP2, the additions of HC sera induced increased MAP-2+ P19 cells phenotype (78.2±1.8% MAP-2+cells) vs. sera of RR-MS patients (47.9±5.9% MAP-2+ cells, p=0.005).
Conclusions: The elevated levels of BMP-2 in the sera of RR-MS patients may contribute to the reduced regeneration capacity of neurons and oligodendrocytes in MS. A positive correlation between BMP-2, -4 and -5 merely in the RR-MS patients group support this reduce tendency of NSCs differentiation in RR-MS. The impaired capacity of sera from RR-MS patients to induce a neuronal phenotype in vitro, suggest that peripheral factors, such as BMPs, play a role in reduced capacity of remyelination and neuroregeneration in MS.
Disclosure:
Moran Penn: nothing to disclose.
Karin Mausner-Fainberg: nothing to disclose
Maya Golan: nothing to disclose.
Arnon Karni: nothing to disclose.
Abstract: EP1438
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Background: Neural stem cells (NSCs) differentiation into functional neurons and oligodendrocytes are insufficient in MS. Bone morphogenic proteins (BMPs) are known to regulate NSCs differentiation and antagonizing BMPs is required for neurons and oligodendrocytes differentiation.
Methods: Sixty six untreated RR-MS patients and 44 matched HC or control cerebrospinal fluid (CSF) donors were included in the study. The levels of BMP-2,-4 &5 and their antagonists, noggin and follistatin were measured in the sera and CSF by ELISA. P19 cells serve as neuronal stem cells (NSC) model, they acquire MAP-2+ neuronal phenotype in response to retinoic acid (RA). Correlation between BMPs, noggin and follistatin was calculated by spearman´s p-value using the Bonferroni´s correction. The effect of sera from RR-MS patients or HC on P19 cells phenotype was examined by stimulating P19 cells with RA, for 4 days and incubation with or without BMP2 neutralizing Ab. MAP-2 expression was examined by immunofluorescence staining and confocal microscopy on day 8.
Results: BMPs, noggin and follistatin, were detected only in the sera but not in the CSF. BMP-2 was significantly higher in sera of RR-MS patients (130.6 ± 47.9 pg/ml) vs. HC (15.6 ± 6.3 pg/ml, p= 0.020). No significant differences between RR-MS patients and HC were found for the other BMPs, or their antagonists. A positive correlation was found between all 3 BMPs only in the RR-MS group (BMP-2 vs. BMP-4, r= 0.52, p= 0.0002; BMP-2 vs. BMP-5, r= 0.52, p= 0.0003; BMP-4 vs. BMP-5, r= 0.61,
p= 0.0001). A positive correlation was found between follistatin and noggin only in HC group (r= 0.61,
p= 0.0035). BMP-2 inhibited the RA-mediated MAP-2 expression on P19 cells. In the presence of RA and BMP2, the additions of HC sera induced increased MAP-2+ P19 cells phenotype (78.2±1.8% MAP-2+cells) vs. sera of RR-MS patients (47.9±5.9% MAP-2+ cells, p=0.005).
Conclusions: The elevated levels of BMP-2 in the sera of RR-MS patients may contribute to the reduced regeneration capacity of neurons and oligodendrocytes in MS. A positive correlation between BMP-2, -4 and -5 merely in the RR-MS patients group support this reduce tendency of NSCs differentiation in RR-MS. The impaired capacity of sera from RR-MS patients to induce a neuronal phenotype in vitro, suggest that peripheral factors, such as BMPs, play a role in reduced capacity of remyelination and neuroregeneration in MS.
Disclosure:
Moran Penn: nothing to disclose.
Karin Mausner-Fainberg: nothing to disclose
Maya Golan: nothing to disclose.
Arnon Karni: nothing to disclose.