Effect of asymmetric dimethylarginine on osteoblastic differentiation

Zhousheng Xiao, Leigh Quarles, Q. Quan Chen, Y. Hui Yu, X. Ping Qu, C. Hong Jiang, H. Wu Deng, Y. Jian Li, H. Hao Zhou

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in renal insufficiency and may be a uremic toxin. To determine whether ADMA inhibits bone metabolism, we investigated the in vitro effect of ADMA on osteoblastic differentiation in mouse bone marrow-derived mesenchymal stem cells (BMSCs). Methods. The effect of ADMA on nitric oxide (NO) production was determined by measuring the stable end product of NO, nitrite, in the culture medium using commercial NO kit. The temporal sequence of osteoblastic differentiation in BMSCs was assessed in the presence and absence of ADMA by measuring alkaline phosphatase (ALP) activity, mineralization, and osteoblast gene expression at 0, 4, 8, 12 days of culture. Results. ADMA (5, 50, 500 μmol · L -1 ) resulted in a dose-dependent decrease in nitrite formation in conditioned media of BMCS cultures, consistent with inhibition of NOS. ADMA treatment was associated with reduced ALP activity, calcium deposition and osteoblast-related gene expression in BMSCs cultures. Concurrent treatment with L-arginine (3600 μmol · L -1 ) reversed the ADMA (500 μmol · L -1 )-mediated decrease in NO production, restored the differentiation potential of BMSCs, and significantly attenuated the down-regulation of Cbfa1 and osteocalcin gene expression by ADMA. Conclusions. ADMA inhibition of the NO-NOS pathway in BMSCs impairs osteoblastic differentiation of mouse BMSC cultures. These studies further support a role of NO in the local regulation of bone metabolism and the possibility that ADMA may act as uremic toxin on bone through its effect to inhibit NO actions in osteoblasts.

Original languageEnglish (US)
Pages (from-to)1699-1704
Number of pages6
JournalKidney International
Volume60
Issue number5
DOIs
StatePublished - Jan 1 2001

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Mesenchymal Stromal Cells
Nitric Oxide
Bone Marrow
Osteoblasts
Nitric Oxide Synthase
Nitrites
Gene Expression
Bone and Bones
Alkaline Phosphatase
N,N-dimethylarginine
Cell Culture Techniques
Osteocalcin
Conditioned Culture Medium
Renal Insufficiency
Culture Media
Arginine
Down-Regulation
Calcium

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Effect of asymmetric dimethylarginine on osteoblastic differentiation. / Xiao, Zhousheng; Quarles, Leigh; Chen, Q. Quan; Yu, Y. Hui; Qu, X. Ping; Jiang, C. Hong; Deng, H. Wu; Li, Y. Jian; Zhou, H. Hao.

In: Kidney International, Vol. 60, No. 5, 01.01.2001, p. 1699-1704.

Research output: Contribution to journalArticle

Xiao, Z, Quarles, L, Chen, QQ, Yu, YH, Qu, XP, Jiang, CH, Deng, HW, Li, YJ & Zhou, HH 2001, 'Effect of asymmetric dimethylarginine on osteoblastic differentiation', Kidney International, vol. 60, no. 5, pp. 1699-1704. https://doi.org/10.1046/j.1523-1755.2001.00011.x
Xiao, Zhousheng ; Quarles, Leigh ; Chen, Q. Quan ; Yu, Y. Hui ; Qu, X. Ping ; Jiang, C. Hong ; Deng, H. Wu ; Li, Y. Jian ; Zhou, H. Hao. / Effect of asymmetric dimethylarginine on osteoblastic differentiation. In: Kidney International. 2001 ; Vol. 60, No. 5. pp. 1699-1704.
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AU - Chen, Q. Quan

AU - Yu, Y. Hui

AU - Qu, X. Ping

AU - Jiang, C. Hong

AU - Deng, H. Wu

AU - Li, Y. Jian

AU - Zhou, H. Hao

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N2 - Background. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in renal insufficiency and may be a uremic toxin. To determine whether ADMA inhibits bone metabolism, we investigated the in vitro effect of ADMA on osteoblastic differentiation in mouse bone marrow-derived mesenchymal stem cells (BMSCs). Methods. The effect of ADMA on nitric oxide (NO) production was determined by measuring the stable end product of NO, nitrite, in the culture medium using commercial NO kit. The temporal sequence of osteoblastic differentiation in BMSCs was assessed in the presence and absence of ADMA by measuring alkaline phosphatase (ALP) activity, mineralization, and osteoblast gene expression at 0, 4, 8, 12 days of culture. Results. ADMA (5, 50, 500 μmol · L -1 ) resulted in a dose-dependent decrease in nitrite formation in conditioned media of BMCS cultures, consistent with inhibition of NOS. ADMA treatment was associated with reduced ALP activity, calcium deposition and osteoblast-related gene expression in BMSCs cultures. Concurrent treatment with L-arginine (3600 μmol · L -1 ) reversed the ADMA (500 μmol · L -1 )-mediated decrease in NO production, restored the differentiation potential of BMSCs, and significantly attenuated the down-regulation of Cbfa1 and osteocalcin gene expression by ADMA. Conclusions. ADMA inhibition of the NO-NOS pathway in BMSCs impairs osteoblastic differentiation of mouse BMSC cultures. These studies further support a role of NO in the local regulation of bone metabolism and the possibility that ADMA may act as uremic toxin on bone through its effect to inhibit NO actions in osteoblasts.

AB - Background. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in renal insufficiency and may be a uremic toxin. To determine whether ADMA inhibits bone metabolism, we investigated the in vitro effect of ADMA on osteoblastic differentiation in mouse bone marrow-derived mesenchymal stem cells (BMSCs). Methods. The effect of ADMA on nitric oxide (NO) production was determined by measuring the stable end product of NO, nitrite, in the culture medium using commercial NO kit. The temporal sequence of osteoblastic differentiation in BMSCs was assessed in the presence and absence of ADMA by measuring alkaline phosphatase (ALP) activity, mineralization, and osteoblast gene expression at 0, 4, 8, 12 days of culture. Results. ADMA (5, 50, 500 μmol · L -1 ) resulted in a dose-dependent decrease in nitrite formation in conditioned media of BMCS cultures, consistent with inhibition of NOS. ADMA treatment was associated with reduced ALP activity, calcium deposition and osteoblast-related gene expression in BMSCs cultures. Concurrent treatment with L-arginine (3600 μmol · L -1 ) reversed the ADMA (500 μmol · L -1 )-mediated decrease in NO production, restored the differentiation potential of BMSCs, and significantly attenuated the down-regulation of Cbfa1 and osteocalcin gene expression by ADMA. Conclusions. ADMA inhibition of the NO-NOS pathway in BMSCs impairs osteoblastic differentiation of mouse BMSC cultures. These studies further support a role of NO in the local regulation of bone metabolism and the possibility that ADMA may act as uremic toxin on bone through its effect to inhibit NO actions in osteoblasts.

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