The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure.

The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure. Research Abstract Details 

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The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure. Abstract Text:

Shozo Yano,Toru Yamaguchi,Ippei Kanazawa,Noriko Ogawa,Kumi Hayashi,Mika Yamauchi,Toshitsugu Sugimoto,Shozo Yano,Toru Yamaguchi,Ippei Kanazawa,Noriko Ogawa,Kumi Hayashi,Mika Yamauchi,Toshitsugu Sugimoto,

BACKGROUND: A relatively high level of serum parathyroid hormone (PTH) is required to maintain normal bone turnover in patients with chronic kidney disease (CKD). 'Uraemic toxins' could cause an impaired response to PTH in bone and result in low turnover bone disease. Since phenylacetic acid (PAA) has been identified as one of the uraemic toxins in patients with CKD and has an inhibiting property of monocyte function, we examined if PAA might inhibit osteoblastic functions in vitro. METHODS: Using mouse osteoblastic MC3T3-E1 cells, we performed BrdU incorporation, real-time PCR, Western blot and stainings to see the effect of PAA. RESULTS: PAA significantly inhibited proliferation in a dose-dependent manner ranging between 0.5 and 5 mM. PAA reduced osteocalcin mRNA level, alkaline phosphatase activity and osteoblastic mineralization. PAA pre-treatment also decreased both PTH-induced cAMP production and extracellular signal-regulated kinase (ERK) phosphorylation. CONCLUSION: PAA, a newly identified uraemic toxin, affects osteoblastic functions such as proliferation, differentiation, mineralization and responsiveness to PTH, indicating that this molecule could play an important role in the pathogenesis of low turnover bone in CKD.

The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure. Publishing Authors By Initials

S Yano,T Yamaguchi,I Kanazawa,N Ogawa,K Hayashi,M Yamauchi,T Sugimoto,S Yano,T Yamaguchi,I Kanazawa,N Ogawa,K Hayashi,M Yamauchi,T Sugimoto,

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The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Nephrology, dialysis, transplantation : official p

VOLUME: 22

Page Numbers: 3160-5

Journal Abbreviation: Nephrol. Dial. Transplant.

ISSN: 0931-0509

DAY: 19

MONTH: 07

YEAR: 2007

The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure. Information

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LANGUAGE: eng

NlmUniqueID: 8706402

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Grant and Affiliation Information for The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure.

AFFILIATION: Department of Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo city, Shimane 693-8501, Japan. syano@med.shimane-u.ac.jp.

Country: England

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MEDLINETA: Nephrol Dial Transplant

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