Negative Skeletal Effects of Locally Produced Adiponectin

Authors

Marcia J. Abbott, Chapman UniversityFollow
Theresa M. Roth, University of California - San Francisco
Linh Ho, University of California - San Francisco
Liping Wang, University of California - San FranciscoFollow
Dylan O'Carroll, University of California - San Francisco
Robert A. Nissenson, University of California - San Francisco

Document Type

Article

Publication Date

7-31-2015

Abstract

Epidemiological studies show that high circulating levels of adiponectin are associated with low bone mineral density. The effect of adiponectin on skeletal homeostasis, on osteoblasts in particular, remains controversial. We investigated this issue using mice with adipocyte-specific over-expression of adiponectin (AdTg). MicroCT and histomorphometric analysis revealed decreases (15%) in fractional bone volume in AdTg mice at the proximal tibia with no changes at the distal femur. Cortical bone thickness at mid-shafts of the tibia and at the tibiofibular junction was reduced (3–4%) in AdTg mice. Dynamic histomorphometry at the proximal tibia in AdTg mice revealed inhibition of bone formation. AdTg mice had increased numbers of adipocytes in close proximity to trabecular bone in the tibia, associated with increased adiponectin levels in tibial marrow. Treatment of BMSCs with adiponectin after initiation of osteoblastic differentiation resulted in reduced mineralized colony formation and reduced expression of mRNA of osteoblastic genes, osterix (70%), Runx2 (52%), alkaline phosphatase (72%), Col1 (74%), and osteocalcin (81%). Adiponectin treatment of differentiating osteoblasts increased expression of the osteoblast genes PPARγ (32%) and C/ebpα (55%) and increased adipocyte colony formation. These data suggest a model in which locally produced adiponectin plays a negative role in regulating skeletal homeostasis through inhibition of bone formation and by promoting an adipogenic phenotype.

Comments

This article was originally published in PLoS ONE, volume 10 , issue 7, in 2015. doi: 10.1371/journal.pone.0134290

Recommended Citation

Abbott MJ, Roth TM, Ho L, Wang L, O’Carroll D, Nissenson RA (2015) Negative Skeletal Effects of Locally Produced Adiponectin. PLoS ONE 10(7): e0134290. doi:10.1371/journal.pone.0134290

Peer Reviewed

1

Copyright

None (Public Domain)

Creative Commons License

This work is licensed under a Creative Commons Public Domain Dedication 1.0 License.