Overexpression of bone morphogenetic protein 7 reduces oligodendrocytes loss and promotes functional recovery after spinal cord injury

被引:11
作者
Liu, Shuxin [1 ]
Zhang, Wei [1 ]
Yang, Lin [1 ]
Zhou, Fan [1 ]
Liu, Peng [2 ]
Wang, Yaping [1 ]
机构
[1] Cent South Univ, Xiangya Hosp 2, Dept Pain Management & Anesthesiol, Changsha, Hunan, Peoples R China
[2] Peoples Liberat Army Joint Logist Support Force 9, Dept Dis Prevent & Control, Changsha, Peoples R China
基金
中国国家自然科学基金;
关键词
BMP7; demyelination; oligodendrocytes; spinal cord injury; BMP7; DIFFERENTIATION; APOPTOSIS; ISCHEMIA; RECEPTOR; DEATH; FATE; PROLIFERATION; DEGENERATION; REGENERATION;
D O I
10.1111/jcmm.16832
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Spinal cord injury (SCI), as a severe disease with no effective therapeutic measures, has always been a hot topic for scientists. Bone morphogenetic protein 7 (BMP7), as a multifunctional cytokine, has been reported to exert protective effects on the nervous system. The present study aimed to investigate the neuroprotective effect and the potential mechanisms of BMP7 on rats that suffered SCI. Rat models of SCI were established by the modified Allen(')s method. Adeno-associated virus (AAV) was injected at T9 immediately before SCI to overexpress BMP7. Results showed that the expression of BMP7 decreased in the injured spinal cords that were at the same time demyelinated. AAV-BMP7 partly reversed oligodendrocyte (OL) loss, and it was beneficial to maintain the normal structure of myelin. The intervention group showed an increase in the number of axons and Basso-Beattie-Bresnahan scores. Moreover, double-labelled immunofluorescence images indicated p-Smad1/5/9 and p-STAT3 in OLs induced by BMP7 might be involved in the protective effects of BMP7. These findings suggest that BMP7 may be a feasible therapy for SCI to reduce demyelination and promote functional recovery.
引用
收藏
页码:8764 / 8774
页数:11
相关论文
共 59 条
[1]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[2]   Review of current evidence for apoptosis after spinal cord injury [J].
Beattie, MS ;
Farooqui, AA ;
Bresnahan, JC .
JOURNAL OF NEUROTRAUMA, 2000, 17 (10) :915-925
[3]   Oligodendrocytes: biology and pathology [J].
Bradl, Monika ;
Lassmann, Hans .
ACTA NEUROPATHOLOGICA, 2010, 119 (01) :37-53
[4]   The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult hippocampal progenitor cell culture [J].
Brederlau, A ;
Faigle, R ;
Elmi, M ;
Zarebski, A ;
Sjöberg, S ;
Fujii, M ;
Miyazono, K ;
Funa, K .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (08) :3863-3875
[5]   Cellular and metabolic alterations in the hippocampus caused by insulin signalling dysfunction and its association with cognitive impairment during aging and Alzheimer's disease: studies in animal models [J].
Calvo-Ochoa, Erika ;
Arias, Clorinda .
DIABETES-METABOLISM RESEARCH AND REVIEWS, 2015, 31 (01) :1-13
[6]   Oligodendroglial apoptosis occurs along degenerating axons and is associated with Fas and p75 expression following spinal cord injury in the rat [J].
Casha, S ;
Yu, WR ;
Fehlings, MG .
NEUROSCIENCE, 2001, 103 (01) :203-218
[7]   Intravenous administration of bone morphogenetic protein-7 after ischemia improves motor function in stroke rats [J].
Chang, CF ;
Lin, SZ ;
Chiang, YH ;
Morales, M ;
Chou, J ;
Lein, P ;
Chen, HL ;
Hoffer, BJ ;
Wang, Y .
STROKE, 2003, 34 (02) :558-564
[8]   Neuroregenerative effects of BMP7 after stroke in rats [J].
Chou, J ;
Harvey, BK ;
Chang, CF ;
Shen, H ;
Morales, M ;
Wang, Y .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2006, 240 (1-2) :21-29
[9]   Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys [J].
Crowe, MJ ;
Bresnahan, JC ;
Shuman, SL ;
Masters, JN ;
Beattie, MS .
NATURE MEDICINE, 1997, 3 (01) :73-76
[10]   Bmp7 regulates branching morphogenesis of the lacrimal gland by promoting mesenchymal proliferation and condensation [J].
Dean, C ;
Ito, M ;
Makarenkova, HP ;
Faber, SC ;
Lang, RA .
DEVELOPMENT, 2004, 131 (17) :4155-4165