Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice

Kristen A. Johnson, Wei Yao, Nancy E Lane, Philippe Naquet, Robert A. Terkeltaub

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Widespread endochondral and intramembranous ectopic bone formation is mediated by extracellular PPi deficiency that develops in ank/ank mice. Herein we report on the rapid condensation into chondrogenic nodules of cultured ank/ank bone marrow stromal cells (BMSCs). We compared the roles of increased chondrogenic potential versus altered osteoblast function in the ank/ank phenotype. To do so, we crossbred ank/ank mice with mice lacking Vanin-1 pantetheinase, which inhibits synthesis of the chondrogenesis regulator glutathione, since we observed increased Vanin-1 expression and pantetheinase activity and decreased glutathione in ank/ank BMSCs. Vnn1-/- BMSCs demonstrated delayed chondrogenesis mediated by increased glutathione. Moreover, increased chondrogenesis of ank/ank BMSCs and increased chondrogenic transdifferentiation and calcification by ank/ank aortic smooth muscle cells and explants were corrected by Vanin-1 knockout. Osteoblastogenesis was accelerated in ank/ank mesenchymal stem cells. However, in cultured ank/ank osteoblasts, Vanin-1 knockout actually increased specific alkaline phosphatase activity and lowered extracellular PPi , and did not correct increased calcification. Moreover, Vanin-1 knockout failed to correct the ank/ank skeletal soft tissue phenotype. Therefore, ank/ank periskeletal soft tissue calcification appears more dependent on altered osteoblastic function than enhanced chondrogenic potential and is not dependent on Vanin-1; however, Vanin-1 regulates chondrogenesis via glutathione metabolism and is critical for accelerated chondrogenesis of ank/ank mesenchymal precursors and Pi donor-driven chondrogenic transdifferentiation and calcification of aortic smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)440-453
Number of pages14
JournalAmerican Journal of Pathology
Volume172
Issue number2
DOIs
StatePublished - Feb 2008

Fingerprint

Chondrogenesis
Mesenchymal Stromal Cells
Glutathione
Osteoblasts
Smooth Muscle Myocytes
Phenotype
Osteogenesis
Alkaline Phosphatase
pantetheinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice. / Johnson, Kristen A.; Yao, Wei; Lane, Nancy E; Naquet, Philippe; Terkeltaub, Robert A.

In: American Journal of Pathology, Vol. 172, No. 2, 02.2008, p. 440-453.

Research output: Contribution to journalArticle

Johnson, Kristen A. ; Yao, Wei ; Lane, Nancy E ; Naquet, Philippe ; Terkeltaub, Robert A. / Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice. In: American Journal of Pathology. 2008 ; Vol. 172, No. 2. pp. 440-453.
@article{9407c4b0d64143129b17c26d51121c93,
title = "Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice",
abstract = "Widespread endochondral and intramembranous ectopic bone formation is mediated by extracellular PPi deficiency that develops in ank/ank mice. Herein we report on the rapid condensation into chondrogenic nodules of cultured ank/ank bone marrow stromal cells (BMSCs). We compared the roles of increased chondrogenic potential versus altered osteoblast function in the ank/ank phenotype. To do so, we crossbred ank/ank mice with mice lacking Vanin-1 pantetheinase, which inhibits synthesis of the chondrogenesis regulator glutathione, since we observed increased Vanin-1 expression and pantetheinase activity and decreased glutathione in ank/ank BMSCs. Vnn1-/- BMSCs demonstrated delayed chondrogenesis mediated by increased glutathione. Moreover, increased chondrogenesis of ank/ank BMSCs and increased chondrogenic transdifferentiation and calcification by ank/ank aortic smooth muscle cells and explants were corrected by Vanin-1 knockout. Osteoblastogenesis was accelerated in ank/ank mesenchymal stem cells. However, in cultured ank/ank osteoblasts, Vanin-1 knockout actually increased specific alkaline phosphatase activity and lowered extracellular PPi , and did not correct increased calcification. Moreover, Vanin-1 knockout failed to correct the ank/ank skeletal soft tissue phenotype. Therefore, ank/ank periskeletal soft tissue calcification appears more dependent on altered osteoblastic function than enhanced chondrogenic potential and is not dependent on Vanin-1; however, Vanin-1 regulates chondrogenesis via glutathione metabolism and is critical for accelerated chondrogenesis of ank/ank mesenchymal precursors and Pi donor-driven chondrogenic transdifferentiation and calcification of aortic smooth muscle cells.",
author = "Johnson, {Kristen A.} and Wei Yao and Lane, {Nancy E} and Philippe Naquet and Terkeltaub, {Robert A.}",
year = "2008",
month = "2",
doi = "10.2353/ajpath.2008.070753",
language = "English (US)",
volume = "172",
pages = "440--453",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice

AU - Johnson, Kristen A.

AU - Yao, Wei

AU - Lane, Nancy E

AU - Naquet, Philippe

AU - Terkeltaub, Robert A.

PY - 2008/2

Y1 - 2008/2

N2 - Widespread endochondral and intramembranous ectopic bone formation is mediated by extracellular PPi deficiency that develops in ank/ank mice. Herein we report on the rapid condensation into chondrogenic nodules of cultured ank/ank bone marrow stromal cells (BMSCs). We compared the roles of increased chondrogenic potential versus altered osteoblast function in the ank/ank phenotype. To do so, we crossbred ank/ank mice with mice lacking Vanin-1 pantetheinase, which inhibits synthesis of the chondrogenesis regulator glutathione, since we observed increased Vanin-1 expression and pantetheinase activity and decreased glutathione in ank/ank BMSCs. Vnn1-/- BMSCs demonstrated delayed chondrogenesis mediated by increased glutathione. Moreover, increased chondrogenesis of ank/ank BMSCs and increased chondrogenic transdifferentiation and calcification by ank/ank aortic smooth muscle cells and explants were corrected by Vanin-1 knockout. Osteoblastogenesis was accelerated in ank/ank mesenchymal stem cells. However, in cultured ank/ank osteoblasts, Vanin-1 knockout actually increased specific alkaline phosphatase activity and lowered extracellular PPi , and did not correct increased calcification. Moreover, Vanin-1 knockout failed to correct the ank/ank skeletal soft tissue phenotype. Therefore, ank/ank periskeletal soft tissue calcification appears more dependent on altered osteoblastic function than enhanced chondrogenic potential and is not dependent on Vanin-1; however, Vanin-1 regulates chondrogenesis via glutathione metabolism and is critical for accelerated chondrogenesis of ank/ank mesenchymal precursors and Pi donor-driven chondrogenic transdifferentiation and calcification of aortic smooth muscle cells.

AB - Widespread endochondral and intramembranous ectopic bone formation is mediated by extracellular PPi deficiency that develops in ank/ank mice. Herein we report on the rapid condensation into chondrogenic nodules of cultured ank/ank bone marrow stromal cells (BMSCs). We compared the roles of increased chondrogenic potential versus altered osteoblast function in the ank/ank phenotype. To do so, we crossbred ank/ank mice with mice lacking Vanin-1 pantetheinase, which inhibits synthesis of the chondrogenesis regulator glutathione, since we observed increased Vanin-1 expression and pantetheinase activity and decreased glutathione in ank/ank BMSCs. Vnn1-/- BMSCs demonstrated delayed chondrogenesis mediated by increased glutathione. Moreover, increased chondrogenesis of ank/ank BMSCs and increased chondrogenic transdifferentiation and calcification by ank/ank aortic smooth muscle cells and explants were corrected by Vanin-1 knockout. Osteoblastogenesis was accelerated in ank/ank mesenchymal stem cells. However, in cultured ank/ank osteoblasts, Vanin-1 knockout actually increased specific alkaline phosphatase activity and lowered extracellular PPi , and did not correct increased calcification. Moreover, Vanin-1 knockout failed to correct the ank/ank skeletal soft tissue phenotype. Therefore, ank/ank periskeletal soft tissue calcification appears more dependent on altered osteoblastic function than enhanced chondrogenic potential and is not dependent on Vanin-1; however, Vanin-1 regulates chondrogenesis via glutathione metabolism and is critical for accelerated chondrogenesis of ank/ank mesenchymal precursors and Pi donor-driven chondrogenic transdifferentiation and calcification of aortic smooth muscle cells.

UR - http://www.scopus.com/inward/record.url?scp=39549111023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39549111023&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2008.070753

DO - 10.2353/ajpath.2008.070753

M3 - Article

C2 - 18187567

AN - SCOPUS:39549111023

VL - 172

SP - 440

EP - 453

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 2

ER -