Abstract
Perineurial-associated brown adipocyte-like cells were rapidly generated during bone morphogenetic protein 2 (BMP2)-induced sciatic nerve remodeling in the mouse. Two days after intramuscular injection of transduced mouse fibroblast cells expressing BMP2 into wild-type mice, there was replication of beta-3 adrenergic receptor+(ADRB3+) cells within the sciatic nerve perineurium. Fluorescence-activated cell sorting and analysis of cells isolated from these nerves confirmed ADRB3+ cell expansion and their expression of the neural migration marker HNK1. Similar analysis performed 4 days after BMP2 delivery revealed a significant decrease in ADRB3+ cells from isolated sciatic nerves, with their concurrent appearance within the adjacent soft tissue, suggesting migration away from the nerve. These soft tissue-derived cells also expressed the brown adipose marker uncoupling protein 1 (UCP1). Quantification of ADRB3- specific RNA in total hind limb tissue revealed a 3-fold increase 2 days after delivery of BMP2, followed by a 70-fold increase in UCP1-specific RNA after 3 days. Expression levels then rapidly returned to baseline by 4 days. Interestingly, these ADRB3+ UCP1+ cells also expressed the neural guidance factor reelin. Reelin+ cells demonstrated distinct patterns within the injected muscle, concentrated toward the area of BMP2 release. Blocking mast cell degranulation-induced nerve remodeling resulted in the complete abrogation of UCP1-specific RNA and protein expression within the hind limbs following BMP2 injection. The data collectively suggest that local BMP2 administration initiates a cascade of events leading to the expansion, migration, and differentiation of progenitors from the peripheral nerve perineurium to brown adipose-like cells in the mouse, a necessary prerequisite for associated nerve remodeling.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 874-885 |
| Number of pages | 12 |
| Journal | Stem cells translational medicine |
| Volume | 1 |
| Issue number | 12 |
| DOIs | |
| State | Published - 2012 |
| Externally published | Yes |
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Keywords
- Adult stem cells
- Beta-3 adrenergic receptor
- Bone
- Bone morphogenetic protein 2
- Brown fat
- Cell migration
- Gene delivery systems in vivo or in vitro
- Perineurium
- Peripheral nerves
- Reelin
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Medicine(all)
Cite this
Transient brown adipocyte-like cells derive from peripheral nerve progenitors in response to bone morphogenetic protein 2. / Salisbury, Elizabeth; Lazard, Zawaunyka W.; Ubogu, Eroboghene E.; Davis, Alan R.; Olmsted-Davis, Elizabeth A.
In: Stem cells translational medicine, Vol. 1, No. 12, 2012, p. 874-885.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transient brown adipocyte-like cells derive from peripheral nerve progenitors in response to bone morphogenetic protein 2
AU - Salisbury, Elizabeth
AU - Lazard, Zawaunyka W.
AU - Ubogu, Eroboghene E.
AU - Davis, Alan R.
AU - Olmsted-Davis, Elizabeth A.
PY - 2012
Y1 - 2012
N2 - Perineurial-associated brown adipocyte-like cells were rapidly generated during bone morphogenetic protein 2 (BMP2)-induced sciatic nerve remodeling in the mouse. Two days after intramuscular injection of transduced mouse fibroblast cells expressing BMP2 into wild-type mice, there was replication of beta-3 adrenergic receptor+(ADRB3+) cells within the sciatic nerve perineurium. Fluorescence-activated cell sorting and analysis of cells isolated from these nerves confirmed ADRB3+ cell expansion and their expression of the neural migration marker HNK1. Similar analysis performed 4 days after BMP2 delivery revealed a significant decrease in ADRB3+ cells from isolated sciatic nerves, with their concurrent appearance within the adjacent soft tissue, suggesting migration away from the nerve. These soft tissue-derived cells also expressed the brown adipose marker uncoupling protein 1 (UCP1). Quantification of ADRB3- specific RNA in total hind limb tissue revealed a 3-fold increase 2 days after delivery of BMP2, followed by a 70-fold increase in UCP1-specific RNA after 3 days. Expression levels then rapidly returned to baseline by 4 days. Interestingly, these ADRB3+ UCP1+ cells also expressed the neural guidance factor reelin. Reelin+ cells demonstrated distinct patterns within the injected muscle, concentrated toward the area of BMP2 release. Blocking mast cell degranulation-induced nerve remodeling resulted in the complete abrogation of UCP1-specific RNA and protein expression within the hind limbs following BMP2 injection. The data collectively suggest that local BMP2 administration initiates a cascade of events leading to the expansion, migration, and differentiation of progenitors from the peripheral nerve perineurium to brown adipose-like cells in the mouse, a necessary prerequisite for associated nerve remodeling.
AB - Perineurial-associated brown adipocyte-like cells were rapidly generated during bone morphogenetic protein 2 (BMP2)-induced sciatic nerve remodeling in the mouse. Two days after intramuscular injection of transduced mouse fibroblast cells expressing BMP2 into wild-type mice, there was replication of beta-3 adrenergic receptor+(ADRB3+) cells within the sciatic nerve perineurium. Fluorescence-activated cell sorting and analysis of cells isolated from these nerves confirmed ADRB3+ cell expansion and their expression of the neural migration marker HNK1. Similar analysis performed 4 days after BMP2 delivery revealed a significant decrease in ADRB3+ cells from isolated sciatic nerves, with their concurrent appearance within the adjacent soft tissue, suggesting migration away from the nerve. These soft tissue-derived cells also expressed the brown adipose marker uncoupling protein 1 (UCP1). Quantification of ADRB3- specific RNA in total hind limb tissue revealed a 3-fold increase 2 days after delivery of BMP2, followed by a 70-fold increase in UCP1-specific RNA after 3 days. Expression levels then rapidly returned to baseline by 4 days. Interestingly, these ADRB3+ UCP1+ cells also expressed the neural guidance factor reelin. Reelin+ cells demonstrated distinct patterns within the injected muscle, concentrated toward the area of BMP2 release. Blocking mast cell degranulation-induced nerve remodeling resulted in the complete abrogation of UCP1-specific RNA and protein expression within the hind limbs following BMP2 injection. The data collectively suggest that local BMP2 administration initiates a cascade of events leading to the expansion, migration, and differentiation of progenitors from the peripheral nerve perineurium to brown adipose-like cells in the mouse, a necessary prerequisite for associated nerve remodeling.
KW - Adult stem cells
KW - Beta-3 adrenergic receptor
KW - Bone
KW - Bone morphogenetic protein 2
KW - Brown fat
KW - Cell migration
KW - Gene delivery systems in vivo or in vitro
KW - Perineurium
KW - Peripheral nerves
KW - Reelin
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UR - http://www.scopus.com/inward/citedby.url?scp=84872923855&partnerID=8YFLogxK
U2 - 10.5966/sctm.2012-0090
DO - 10.5966/sctm.2012-0090
M3 - Article
VL - 1
SP - 874
EP - 885
JO - Stem cells translational medicine
JF - Stem cells translational medicine
SN - 2157-6564
IS - 12
ER -