TY - JOUR
T1 - Bone and joint neuropathy in rats with type-2 diabetes
AU - Ahmad, Tashfeen
AU - Ugarph-Morawski, Anna
AU - Li, Jian
AU - Bileviciute-Ljungar, Indre
AU - Finn, Anja
AU - Östenson, Claes Göran
AU - Kreicbergs, Andris
N1 - Funding Information:
We thank Prof. Elvar Theodorsson from the Department of Biomedicine and Surgery, Section for Clinical Chemistry, Linköping University for providing the CGRP and SP antisera for RIA, and Dr. Per Bjellerup from the Department of Clinical Chemistry, Huddinge University Hospital for radioiodine-labelling of peptides. This study was supported by grants from the Karolinska Institute, Swedish Medical Research Council (00034, 13107), the Swedish Diabetes Association and the Aga Khan University, Karachi, Pakistan.
Funding Information:
FUNDING: Karolinska Institute, Stockholm, Sweden; Swedish Medical Research Council; the Swedish Diabetes Association and the Aga Khan University, Karachi, Pakistan.
PY - 2004/6/15
Y1 - 2004/6/15
N2 - We have previously demonstrated that Goto-Kakizaki (GK) rats with spontaneous type-2 diabetes and peripheral neuropathy exhibit regional osteopathic changes. In the present study on 18 GK rats and 21 control Wistar rats, the occurrence of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the autonomic neuropeptide Y (NPY) was analysed in bone and joints, dorsal root ganglia and lumbar spinal cord by immunohistochemistry and radioimmunoassay (RIA). Immunohistochemistry disclosed a predominance of immunoreactivities in vessel-related nerve fibers, although some were also seen in free terminals. While SP, CGRP and NPY in periosteum, cortical bone and synovium was confined to neuronal tissue, the bone marrow in addition exhibited an abundance of NPY-positive megakaryocytes. Apart from this cellular source of NPY, the observations suggest that the three neuropeptides analysed in bone and joints are of neuronal origin. Quantification by RIA showed a significant decrease of NPY in cortical bone (-36%), bone marrow (-66%) and ankle (-29%) of GK rats. CGRP was decreased in the spinal cord (-19%) and dorsal root ganglia (-26%) but was unchanged in bone and joints, as with SP. Given the suggested anabolic role of NPY and CGRP on bone, neuropeptidergic deficit in diabetes may prove to be an important factor underlying the development of regional osteopenia.
AB - We have previously demonstrated that Goto-Kakizaki (GK) rats with spontaneous type-2 diabetes and peripheral neuropathy exhibit regional osteopathic changes. In the present study on 18 GK rats and 21 control Wistar rats, the occurrence of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the autonomic neuropeptide Y (NPY) was analysed in bone and joints, dorsal root ganglia and lumbar spinal cord by immunohistochemistry and radioimmunoassay (RIA). Immunohistochemistry disclosed a predominance of immunoreactivities in vessel-related nerve fibers, although some were also seen in free terminals. While SP, CGRP and NPY in periosteum, cortical bone and synovium was confined to neuronal tissue, the bone marrow in addition exhibited an abundance of NPY-positive megakaryocytes. Apart from this cellular source of NPY, the observations suggest that the three neuropeptides analysed in bone and joints are of neuronal origin. Quantification by RIA showed a significant decrease of NPY in cortical bone (-36%), bone marrow (-66%) and ankle (-29%) of GK rats. CGRP was decreased in the spinal cord (-19%) and dorsal root ganglia (-26%) but was unchanged in bone and joints, as with SP. Given the suggested anabolic role of NPY and CGRP on bone, neuropeptidergic deficit in diabetes may prove to be an important factor underlying the development of regional osteopenia.
KW - Calcitonin gene-related peptide
KW - Diabetic neuropathy
KW - Diabetic osteopathy
KW - Goto-Kakizaki rat
KW - Neuropeptide Y
KW - Neuropeptides
KW - Substance P
UR - http://www.scopus.com/inward/record.url?scp=1842785714&partnerID=8YFLogxK
U2 - 10.1016/j.regpep.2003.12.008
DO - 10.1016/j.regpep.2003.12.008
M3 - Article
C2 - 15093698
AN - SCOPUS:1842785714
SN - 0167-0115
VL - 119
SP - 61
EP - 67
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 1-2
ER -