Abolition of chondral mineralization by group III metabotropic glutamate receptors expressed in rodent cartilage

Liyang Wang, Eiichi Hinoi, Akihiro Takemori, Takeshi Takarada, Yukio Yoneda

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

1. Previous studies have demonstrated the functional expression by osteoblasts of glutamate (Glu) signaling machineries responsible for the stimulation of cell proliferation and differentiation in bone, while there is no information available on the expression of the Glu signaling system by cartilage to date. 2. In cultured mouse embryonic metatarsals isolated before vascularization, chondral mineralization was almost completely inhibited in the presence of the group III metabotropic Glu receptor (mGluR) agonist L-(1)-2-amino-4-phosphonobutyrate (L-AP4) in a manner sensitive to an antagonist, with the total length being unchanged. 3. A group II mGluR agonist was similarly more effective in inhibiting the mineralization than a group I mGluR agonist, while none of ionotropic GluR agonists drastically affected the mineralization. 4. Both histological and in situ hybridization analyses revealed that L-AP4 specifically inhibited chondral mineralization, without apoptotic cell death, in cultured metatarsals. 5. In addition to the constitutive expression of mRNA for particular mGluRs in both cultured mouse metatarsals and rat costal chondrocytes, L-AP4 significantly inhibited the accumulation of cyclic AMP by forskolin and parathyroid hormone in a manner sensitive to a group III mGluR antagonist in cultured chondrocytes. 6. Moreover, L-AP4 drastically inhibited the expression of osteopontin mRNA in both cultured metatarsals and chondrocytes. 7. These results suggest that Glu may at least in part play a role as a signal mediator in mechanisms associated with chondral mineralization through the group III mGluR subtype functionally expressed by chondrocytes in rodent cartilage.

Original languageEnglish
Pages (from-to)732-743
Number of pages12
JournalBritish Journal of Pharmacology
Volume146
Issue number5
DOIs
Publication statusPublished - Nov 2005
Externally publishedYes

Keywords

  • Alkaline phosphatase
  • Chondrocytes
  • Glutamate
  • Metatarsals
  • Mineralization
  • Oosteopontin
  • Parathyroid hormone
  • RT-PCR
  • cAMP
  • mGluRs

ASJC Scopus subject areas

  • Pharmacology

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