Expression and regulation of osteoprotegerin in adipose tissue.
OBJECTIVE
Osteoprotegerin (OPG), a potent inhibitor of osteoclastic bone resorption, has a variety of biological functions that include anti-inflammatory effects. Adipocytes and osteoblasts share a common origin, and the formation of new blood vessels often precedes adipogenesis in developing adipose tissue microvasculature. We examined whether OPG is secreted from adipocytes, therefore contributing to the prevention of neovascularization and protecting the vessels from intimal inflammation and medial calcification.


METHODS
The mRNA expression of OPG and receptor activator of NF-kappaB ligand (RANKL) was measured in differentiated 3T3L1 adipocytes and adipose tissues.


RESULTS
OPG mRNA expression increased with the differentiation of 3T3L1 adipocytes, while RANKL expression was not significantly altered. OPG mRNA was expressed at higher levels in white adipose tissue than in brown adipose tissue and was most abundant in the epididymal portion. In differentiated 3T3L1 adipocytes, Rosiglitazone and insulin reduced the OPG/RANKL expression ratio in a dose- and time- dependent manner. In contrast, tumor necrosis factor-alpha (TNF-alpha) increased the expression of both OPG and RANKL in a time-dependent manner. The OPG/RANKL ratio was at a maximum two hours after TNF-alpha treatment and then returned to control levels. Furthermore, OPG was abundantly secreted into the media after transfection of OPG cDNA with Phi C31 integrase into 3T3L1 cells.


CONCLUSIONS
Our results indicate that OPG mRNA is expressed and regulated in the adipose tissue. Considering the role of OPG in obesity-associated inflammatory changes in adipose tissue and vessels, we speculate that OPG may have both a protective function against inflammation and anti-angiogenic effects on adipose tissue.
An
Juan-Ji
JJ
Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea.
Han
Dong-He
DH
Kim
Dol-Mi
DM
Kim
Se-Hwa
SH
Rhee
Yumie
Y
Lee
Eun-Jig
EJ
Lim
Sung-Kil
SK
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D053244:Osteoprotegerin; D053245:RANK Ligand; D045162:Thiazolidinediones; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone