Traumatic injury-induced BMP7 expression in the adult rat spinal cord

Setoguchi, Takao; Yone, Kazunori; Matsuoka, Eiji; Takenouchi, Hironori; Nakashima, Kinichi; Sakou, Takashi; Komiya, Setsuro; Izumo, Shuji

doi:10.1016/s0006-8993(01)03123-7

Cited by 113 publications

(87 citation statements)

References 43 publications

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“…An increase in the expression of BMP2 and BMP7 has been shown in the adult spinal cord after injury. 28,29 Consistent with this observation, BMP7 was upregulated after sciatic nerve injury in this study. AdBMP7 transduction to the sciatic nerves further increase BMP7 expression and is beneficial to nerve, myelin and hind limb functions.…”

Section: Discussionsupporting

confidence: 89%

Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats

Pan

et al. 2010

Gene Ther

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Bone morphogenetic proteins (BMPs), members of the transforming growth factor-b subfamily, function as instructive signals for neuronal lineage commitment and promote neuronal differentiation. However, the mechanism of BMP7 action in vivo after peripheral nerve injury is poorly understood. This study examines the efficacy of gene transfer of adenoviral (Ad) BMP7 on peripheral neuropathy. Transgene expression was found in both Ad-infected sciatic nerves and their respective remote neurons, indicating Ad transduction by a retrograde transport. After AdBMP7 infection to nerves, the sciatic nerves were crushed or transected. Hind limb functional behavior, including rotarod test and sciatic functional index, were conducted in rats weekly after nerve injury. Interestingly, enhanced BMP7 expression significantly improved hind limb functional recovery in AdBMP7-transduced rats when compared with AdGFPtransduced nerve-crushed or transected rats. Furthermore, AdBMP7 transduction reduced injury-induced macrophage activation, nerve demyelination and axonal degeneration. By contrast, AdBMP7 infection did not affect the hyperalgesia paw-withdrawal latency after nerve injury. We further examined the effect of AdBMP7 infection on sciatic nerve explant and Schwann cell cultures. Enhanced cell proliferation was significantly increased by AdBMP7 transduction in both cultures. Taken together, BMP7 overexpression by Ad gene transfer was beneficial in both nerves and Schwann cells on functional recovery after sciatic nerve injury in rats.

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Section: Discussionsupporting

confidence: 89%

Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats

Pan

et al. 2010

Gene Ther

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“…In the transplantation models, cultured GPCs, neuroepithelial cells, or neural stem cells transplanted into the lesioned spinal cords predominately become glia in response to SCI [11,12]. This may reflect that the molecular cues from SCI selectively induce transplanted cells toward the glial direction [14]. On the other hand, the cell culture conditions may predetermine the differentiation potentials toward the glial lineage.…”

Section: Discussionmentioning

confidence: 99%

“…However, the majority of surviving transplanted neural stem cells, glial progenitor cells (GPCs), or NPCs differentiate into astroglial phenotypes in the lesioned spinal cord [11,12]. The molecular nature of differentiation of transplanted neural stem cells toward glial cell direction remains largely unknown but could to some extent be due to the antineurogenic function of bone morphogenetic proteins (BMPs) released after SCI [13,14]. Indeed, transplantation of fetal neural precursor cells overexpressing BMP inhibitor promoted differentiation of neural precursor cells into neurons and oligodendrocytes and, more significantly, increased functional recovery in recipient mice after SCI [14].…”

Section: Introductionmentioning

confidence: 99%

“…The molecular nature of differentiation of transplanted neural stem cells toward glial cell direction remains largely unknown but could to some extent be due to the antineurogenic function of bone morphogenetic proteins (BMPs) released after SCI [13,14]. Indeed, transplantation of fetal neural precursor cells overexpressing BMP inhibitor promoted differentiation of neural precursor cells into neurons and oligodendrocytes and, more significantly, increased functional recovery in recipient mice after SCI [14]. In addition, transplantation of other cell types, such as olfactory ensheathing cells and Schwann cells, into the injured spinal cord was demonstrated to increase tissue regenerative capacity, even though the structural and functional recovery was relatively modest [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Early Response of Endogenous Adult Neural Progenitor Cells to Acute Spinal Cord Injury in Mice

Chi

et al. 2006

Stem Cells

110

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Adult neural progenitor cells (NPCs) are an attractive source for functional replacement in neurodegenerative diseases and traumatic injury to the central nervous system (CNS). It has been shown that transplantation of neural stem cells or NPCs into the lesioned region partially restores CNS function. However, the capacity of endogenous NPCs in replacement of neuronal cell loss and functional recovery of spinal cord injury (SCI) is apparently poor. Furthermore, the temporal and spatial response of endogenous adult NPCs to SCI remains largely undefined. To this end, we have analyzed the early organization, distribution, and potential function of NPCs in response to SCI, using nestin enhancer (promoter) controlled LacZ reporter transgenic mice. We showed that there was an increase of NPC proliferation, migration, and neurogenesis in adult spinal cord after traumatic compression SCI. The proliferation of NPCs detected by 5-bromodeoxyuridine incorporation and LacZ staining was restricted to the ependymal zone (EZ) of the central canal. During acute SCI, NPCs in the EZ of the central canal migrated vigorously toward the dorsal direction, where the compression lesion is generated. The optimal NPC migration occurred in the adjacent region close to the epicenter. More significantly, there was an increased de novo neurogenesis from NPCs 24 hours after SCI. The enhanced proliferation, migration, and neurogenesis of (from) endogenous NPCs in the adult spinal cord in response to SCI suggest a potential role for NPCs in attempting to restore SCI-mediated neuronal dysfunction.

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“…However, recent data demonstrate that it also has a physiological function as a type I receptor in BMP signaling (ten Dijke et al, 1994;Zhang et al, 2003). The presence of BMPs has been confirmed in a variety of organs and tissues such as bone and kidney (Li and Wozney, 2001;Simic and Vukicevic, 2005), and their function in embryonic development, regulation of cell differentiation, specification of mesoderm-derived cells, and tooth morphogenesis has been investigated (Hogan, 1996;Setoguchi et al, 2001;Plikus et al, 2005). BMP7, also known as osteogenic protein-1, has been reported to be involved in the development of the kidney, nervous system, skeletal muscle, and eyes (Dudley et al, 1995;Luo et al, 1995;Arkell and Beggington, 1997;Furuta and Hogan, 1998;Gupta et al, 2000;Zhang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Expression of BMP7 is associated with resistance to diabetic stress: Comparison among mouse salivary glands

Izumi

Watanabe

Sawaki

et al. 2008

European Journal of Pharmacology

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We determined mRNA levels of bone morphogenetic protein 7 (BMP7), a growth and differentiation factor belonging to the transforming growth factor-β superfamily, in the salivary glands of mice with streptozotocin (200 mg/kg, i.p.)-induced diabetes. We also examined the effects of BMP7 on secretion of saliva and degenerative change in salivary glands in diabetic mice. In normal mice, BMP7 mRNA levels were high in the submandibular gland and low in the parotid gland, while in diabetic mice, levels were significantly decreased in the parotid gland, but not in the submandibular gland. No significant difference was observed in mRNA levels of BMP receptors between normal and diabetic mice. In diabetic mice, pilocarpine (4 mg/kg, i.p.)-stimulated salivary secretion showed a remarkable decrease in both parotid and submandibular gland, although degree of reduction was smaller in the latter. N otable degeneration with vacuolation and atrophy was also found in parotid gland, whereas degeneration of submandibular gland was slight. Administration of BMP7 (50 and 100 µg/kg, i.v.) in diabetic mice induced a significant increase in salivary secretion, with rate of recovery higher in parotid gland than in submandibular gland. In diabetic mice, BMP7 also exhibited a powerful protective effect in degenerated salivary gland, especially in parotid gland. These results suggest that BMP7 acts to prevent diabetic damage in salivary gland, and that its cytoprotective effect is closely correlated with mRNA levels in tissue.

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Traumatic injury-induced BMP7 expression in the adult rat spinal cord

Cited by 113 publications

References 43 publications

Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats

Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats

Early Response of Endogenous Adult Neural Progenitor Cells to Acute Spinal Cord Injury in Mice

Expression of BMP7 is associated with resistance to diabetic stress: Comparison among mouse salivary glands

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