title: t10c12-CLA maintains higher bone mineral density during aging by modulating osteoclastogenesis and bone marrow adiposity.
abstract: Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism. Earlier, we showed that CLA (equal mixture of c9t11-CLA and t10c12-CLA) could protect age-associated bone loss by modulating inflammatory markers and osteoclastogenesis. Since, c9t11-CLA and t10c12-CLA isomers differentially regulate functional parameters and gene expression in different cell types, we examined the efficacy of individual CLA isomers against age-associated bone loss using 12 months old C57BL/6 female mice fed for 6 months with 10% corn oil (CO), 9.5% CO + 0.5% c9t11-CLA, 9.5% CO + 0.5% t10c12-CLA or 9.5% CO + 0.25% c9t11-CLA + 0.25% t10c12-CLA. Mice fed a t10c12-CLA diet maintained a significantly higher bone mineral density (BMD) in femoral, tibial and lumbar regions than those fed CO and c9t11-CLA diets as measured by dual-energy-X-ray absorptiometry (DXA). The increased BMD was accompanied by a decreased production of osteoclastogenic factors, that is, RANKL, TRAP5b, TNF-alpha and IL-6 in serum. Moreover, a significant reduction of high fat diet-induced bone marrow adiposity was observed in t10c12-CLA fed mice as compared to that of CO and c9t11-CLA fed mice, as measured by Oil-Red-O staining of bone marrow sections. In addition, a significant reduction of osteoclast differentiation and bone resorbing pit formation was observed in t10c12-CLA treated RAW 264.7 cell culture stimulated with RANKL as compared to that of c9t11-CLA and linoleic acid treated cultures. In conclusion, these findings suggest that t10c12-CLA is the most potent CLA isomer and it exerts its anti-osteoporotic effect by modulating osteoclastogenesis and bone marrow adiposity.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio, Texas 78229-3900, USA. rahmanm@uthscsa.edu
authors.forename: Md M
authors.initials: MM
authors.lastname: Rahman
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Williams
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fernandes
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000187:drug effects*; D000375:Aging / Q000187:drug effects*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000097:blood / Q000473:pathology; D002460:Cell Line; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D053245:RANK Ligand / Q000097:blood; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D007527:Isoenzymes; D044243:Linoleic Acids, Conjugated; D053245:RANK Ligand; C496197:trans-10,cis-12-conjugated linoleic acid; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase