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

Br J Pharmacol. 2005 Nov;146(5):732-43. doi: 10.1038/sj.bjp.0706358.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Calcification, Physiologic / physiology*
  • Cartilage / metabolism
  • Cartilage / physiology*
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • DNA Primers
  • Female
  • Mice
  • Organ Culture Techniques
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA Primers
  • Receptors, Metabotropic Glutamate
  • Cyclic AMP