Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord.
Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.
Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun, Jilin Province, China.
Peng
P
Xia
Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun, Jilin Province, China.
Su
S
Pan
Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun, Jilin Province, China.
Jieping
J
Cheng
Department of Endocrinology, Second Hosptal, Jilin University, Changchun, Jilin Province, China.
Maoguang
M
Yang
Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun, Jilin Province, China.
Zhiping
Z
Qi
Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun, Jilin Province, China.
Tingting
T
Hou
Department of Spine Surgery, Orthopedics Hospital, Second Hosptal, Jilin University, Changchun, Jilin Province, China.
Xiaoyu
X
Yang
NSFC grant; bone marrow mesenchymal stem cells; cell transplantation; microtubule-associated protein 1B; nerve regeneration; neural regeneration; phosphorylation; protein phosphatase 2A; signal transduction; spinal cord injury