CART deficiency increases body weight but does not alter bone strength

S. M. Bartell, C. M. Isales, C. A. Baile, M. J. Kuhar, Mark W. Hamrick

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The regulation of bone metabolism mediated by leptin is a complex process that is not clearly understood. Recent studies suggest that CART (cocaine-amphetamine related transcript) is a significant neuronal co-factor when combined with leptin. CART deficiency is thought to result in low trabecular bone mass, but since leptin exerts contrasting effects on trabecular and cortical bone it is possible that cortical bone may not respond to the absence of CART signaling in the same manner as trabecular bone. We tested the hypothesis that CART deficiency decreases cortical bone mass, density, and strength by examining femora of adult wild-type mice (CART+/+) and CART-deficient mice (CART-/ -). DEXA densitometry (PIXImus system) was used to measure whole-bone mineral content (BMC) and mineral density (BMD) from right femora, and pQCT used to calculale densitometric and geometric parameters from the femur midshaft. Femora were also tested in three-point bending, and sections of the tibia analyzed histologically to determine bone marrow adipocyte density (N.At./M.Ar) and endocortical osteoclast number (N.Oc/B.Pm). The control mice weighed less than the mice lacking CART (P<0.001), but mechanical testing data showed no differences (p>0.05) in ultimate force, energy to fracture, stiffness, or intrinsic properties such as ultimate stress, ultimate strain, or modulus. CART-deficient mice did not differ from normal controls in whole-femur BMC (p=0.09), BMD (p=0.19), midshaft cortical bone thickness (p=0.67), midshaft cortical bone area (p=0.59) or N.Oc/ B.Pm (p=0.94), although CART deficiency was associated with a three-fold increase in bone marrow adipocyte density (p<0.001). Our data suggest that while the central, neuroendocrine regulation of bone mass via CART signaling may have effects on trabecular mass, absence of CART expression does not significantly alter cortical bone geometry, density, or strength.

Original languageEnglish (US)
Pages (from-to)146-153
Number of pages8
JournalJournal of Musculoskeletal Neuronal Interactions
Issue number2
StatePublished - Jun 1 2008


  • Adipocyte
  • Body weight
  • Bone mass
  • Cortical bone
  • Leptin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Orthopedics and Sports Medicine


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