Table 3.

Therapeutic and genetic targeting of BMP signaling in SCI in in vivo models

Treatment	SCI model	Effects	Ref.
BMP7	Rats	BMP7 promoted neuroprotection via an increase in the number of surviving neurons, in part, via increased p38 non-canonical signaling	[24]
Agmatine	Mice	It augmented BMP7 expression, reduced collagen scar formation, and improved BBB scores	[30]
Agmatine	Mice	It reduced neuronal cell death and scar formation, leading to improved locomotive function. This effect was achieved, in part, via increased expression of BMP2/7 in neurons and oligodendrocytes, and decreased expression of BMP4 in the damaged site	[31]
Conditional deletion of astrocytic BMPR1A and 1B	Mice	Knockouts of astrocytic BMPR1A cause reduction in astrocytic hypertrophy, decrease in axonal density, and enhancement of the inflammatory response. In contrast, knockouts of astrocytic BMPR1B increase astrocytic hypertrophy and reduce lesion size and glial scar formation post-SCI	[26]
Transplantation of OPCs expressing BMPR1A, 1B, and 2	Rats	Transplantation of OPCs expressing (BMPR1A, 1B, and 2) into rat spinal cord led to their differentiation into astrocytes	[40]
Administration of AAV vector encoding BMP4	Mice	Intra-thecal administration of AAV vector encoding BMP4 led to Smad1 activation in dorsal motoneuron and increased axonal regrowth after SCI	[42]
Conditional knockout of β1-integrin in ependymal stem cells	Mice	Conditional knockout of β1-integrin in ependymal stem cells increased the movement of BMPR1B into lipid rafts while enhancing BMP signaling (canonical and non-canonical) and glial scar formation	[39]
Noggin	Rats	Administration of recombinant mouse noggin intra-thecally improved locomotive function post-SCI and enhanced axonal regrowth	[23]
Noggin	Rats	Noggin treatment reduced BMP2/4 expression and improved motor scored post-SCI	[29]
Transplantation of Smad6, Smad7, or noggin expressing NPCs	Mice	It promoted differentiation of NPCs into oligodendrocytes and neurons but inhibited their differentiation into astrocytes, leading to improvement of BBB scores in mice post-SCI	[38]
Transplantation of noggin expressing neuronal stem Cells	Rats	It led to macrophage infiltration and widening of lesion size, but prevented astrocytic differentiation post-SCI	[16]
BAMBI	Rats	Overexpression of BAMBI inhibited inflammation and promoted autophagy post-SCI	[54]
BMP2	Rats	Intra-thecal administration of rhBMP2 resulted in increases in expression of p-Smad1, 5, and 8 in most spinal cord cell types	[32]

BMP: bone morphogenic protein; SCI: spinal cord injury; OPCs: oligodendrocyte precursor cells; NSCs: neural stem cells; BBB: Basso, Beattie, and Bresnahan; BMPR: BMP receptor; BAMBI: BMP and activin membrane-bound inhibitor; AAV: adeno-associated virus