title: Negative Skeletal Effects of Locally Produced Adiponectin.
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.
authors.affiliation: Endocrine Research Unit, VA Medical Center and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, United States of America; Department of Health Sciences and Kinesiology, Crean College of Health and Behavioral Sciences, Chapman University, Orange, CA, United States of America.
authors.forename: Marcia J
authors.initials: MJ
authors.lastname: Abbott
authors.affiliation: Endocrine Research Unit, VA Medical Center and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Roth
authors.affiliation: Endocrine Research Unit, VA Medical Center and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Linh
authors.initials: L
authors.lastname: Ho
authors.affiliation: Endocrine Research Unit, VA Medical Center and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Endocrine Research Unit, VA Medical Center and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Dylan
authors.initials: D
authors.lastname: O'Carroll
authors.affiliation: Endocrine Research Unit, VA Medical Center and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Nissenson
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology
chemical_list: D052242:Adiponectin