Glutamate Signalling In Bone Of Ovariectomized Osteoporosis Rats And The Effects Of Yigu Capsule On It

Objective:Bone is a highly innervation,glutamate signalling in bone plays an important role in re-modified,the study focus on glutamate signalling in bone of ovariectomized osteoporosis rats and the effects of Yigu Capsule on it.Methods:Thirty-six 10-months Sprague-Dawley female rats were randomly divided into 9 sham-operated groups and 27 model groups,the latter then were randomly divided into three groups:model group,Yigu Capsule low-dose group,Yigu Capsule high-dose group.By dual-energy X-ray measurement and analysis of bone tissue morphology with immuno-histochemical technique and image analysis,as well as FQ-PCR and ELISA techniques.Bone mineral density was observed,pathological changes in bone tissue,serum E₂ assaying,and investigated the change of components of glutamate signalling in the distal femur in OP by the intervention of Yigu Capsule.Results:(1) Yigu capsule can increase the level of serum E₂,improve bone mineral density and bone tissue pathology ofovariectomized osteoporosis rats.(2) Endogenous ligand glutamate and its receptors in femur of sham-operated groups are observed.Glutamate is widely distributed in chondrocyte,osteocytes,in bone marrow cells, osteoblasts and a few osteoclasts in the bone reconstructive unit.NMDAR1,functional subunits of glutamate receptors,is mainly distributed in bone marrow cells,osteocytes and osteoblasts along bone trabecula;but NMDAR2a mainly in bone lining cells,osteoblasts,cells in bone marrow and a few osteocytes;NMDAR2b is found in bone marrow cells,as well as osteoblasts at the edge of trabecular bone,and a few osteocytes;mGluR1 mainly distributed in the area of bone marrow cells,osteocytes,osteoblasts and osteoclasts of trabecular bone;The positive labeled mGluR4 is mainly distributed in areas of bone marrow cells,chondrocyte,osteoclasts and osteoblasts in the bone reconstructive unit;while mGluR2/3 is widely found in chondrocyte, bone marrow cells and osteoclasts of trabecular bone.The glutamate signal pathway is disorder in ovariectomized osteoporosis rats:Distribution of endogenous glutamate decline,positive labeled of mGluR2/3 in the distal femur is almost loss, positive marked mGluR1 reduced,and positive marking NMDAR2b and NMDAR2a significantly increased,the positive labeled of NMDAR1,mGluR4 remain unchanged.Yigu capsule can improve local markings of glutamate,mGluR1 and mGluR2/3 in the bone tissue, also increase the markings of NMDAR1,otherwise NMDAR2b reduced.The immune positive labeled of mGluR4 and NMDAR2a have no significant impact.(3) the level of cAMP in bone tissue decreased,at the same time the expression of AC,Runx2 mRNA also decreased in ovariectomized osteoporosis rats,the Yigu capsule can increase level of cAMP and the expression of AC,Runx2 mRNA.Conclusion:(1)Ovariectomized osteoporosis rats can be treated with Yigu capsule.(2) The glutamate signal pathway is disorder in bone of ovariectomized osteoporosis rats,Yigu capsule can modulate the distribution and density of the composition of glutamate signaling and coordinate different molecule signals in response to the relationship,by which reversing the direction of high conversion remodeling of the ovariectomized osteoporosis rats.These data provide valuable insight into the mechanisms by which Yigu capsule may have relation with the prevention and treatment of osteoporosis...