Conjugated linoleic acid inhibits osteoclast differentiation of RAW264.7 cells by modulating RANKL signaling.
Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis, periodontitis, and osteoporosis. Inflammation-induced bone loss of this sort results from increased numbers of bone-resorbing osteoclasts. Numerous studies have indicated that conjugated linoleic acid (CLA) positively influences calcium and bone metabolism. Gene-deletion studies have shown that receptor activator of nuclear factor-kappaB ligand (RANKL) is one of the critical mediators of osteoclastogenesis. In this report, we examine the ability of CLA to suppress RANKL signaling and osteoclastogenesis in RAW264.7 cells, a murine monocytic cell line. Treatment of these cells with RANKL activated nuclear factor-kappaB (NF-kappaB), and preexposure of the cells to CLA significantly suppressed RANKL-induced NF-kappaB activation, including phosphorylation of I-kappaBalpha, degradation of I-kappaBalpha, and nuclear translocation of p65. RANKL induced osteoclastogenesis in these monocytic cells, and CLA inhibited RANKL-induced tumor necrosis factor-alpha production and osteoclast differentiation, including osteoclast-specific genes such as tartrate-resistant acid phosphatase, cathepsin K, calcitonin receptor, and matrix metalloproteinase-9 expression and osteoclast-specific transcription factors such as c-Fos, nuclear factor of activated T-cells expression, and bone resorption pit formation. CLA also inhibited RANKL-induced activation of mitogen-activated protein kinase p38 but had little effect on c-Jun N-terminal kinase activation. Collectively, these data demonstrate for the first time that CLA inhibits osteoclastogenesis by modulating RANKL signaling. Thus, CLA may have important therapeutic implications for the treatment of bone diseases associated with enhanced bone resorption by excessive osteoclastogenesis.
Rahman MM, Bhattacharya A, Fernandes G
J. Lipid Res. Aug 2006
PMID: 16702601 | Free Full Text
Regulation of osteoblast and adipocyte differentiation from human mesenchymal stem cells by conjugated linoleic acid.
Conjugated linoleic acid (CLA) describes a group of isomers of linoleic acid and has variable effects on bone formation and adiposity in vivo and in vitro. The variability may be due to individual effects of the predominant bioactive 9cis,11trans (9,11) and 10trans,12cis (10,12) CLA isomers. Osteoblasts and adipocytes are derived from mesenchymal stem cells (MSCs), and bone loss is accompanied by an increase in marrow adiposity. Osteoblast differentiation from MSCs requires activation of Wnt/beta-catenin signaling by Wnt10b, which inhibits adipocyte differentiation by suppressing CCAAT/enhancer-binding protein (C/EBP) alpha. The objective of this study was to determine if 9,11 and 10,12 CLA affect osteoblast and adipocyte differentiation from MSCs and to determine whether any effects are associated with changes in Wnt10b and C/EBPalpha expression. Osteoblast differentiation was assessed by calcium deposition, alkaline phosphatase (ALP) activity, and the expression of Wnt10b, runx2 and osteocalcin. Adipocyte differentiation was assessed by oil red O staining and C/EBPalpha, PPARgamma and FABP4 expression. Compared to vehicle, 9,11 CLA decreased calcium deposition ( approximately 15%), increased oil red O staining ( approximately 21-28%) and increased FABP4 (AP2) expression ( approximately 58-75%). In contrast, 10,12 CLA increased calcium deposition ( approximately 12-60%), ALP activity ( approximately 2.1-fold) and the expression of Wnt10b ( approximately 60-80%) and osteocalcin ( approximately 90%), but decreased oil red O staining ( approximately 30%) and the expression of C/EBPalpha ( approximately 24-38%) and PPARgamma ( approximately 60%) (P<.05). Thus, our findings demonstrate isomer-specific effects of CLA on MSC differentiation, and suggest that 10,12 CLA may be a useful therapeutic agent to promote osteoblast differentiation from MSCs.
Platt ID, El-Sohemy A
J. Nutr. Biochem. Dec 2009
Conjugated linoleic acid prevents growth attenuation induced by corticosteroid administration and increases bone mineral content in young rats.
Corticosteroids are a common therapy in many disease states, despite frequent and potentially serious side effects. Nutritional supplementation with conjugated linoleic acid (CLA) has been shown to increase fat-free mass, whereas supplementation with n-3 and n-6 fatty acids has been shown to increase bone mineral density (BMD). To determine whether CLA can attenuate the side effects of 8 weeks of corticosteroid administration, we randomized twenty-four 5-week-old male Sprague-Dawley rats into 1 of 4 groups: control; control + methylprednisolone (7 mg.kg-1.week-1); CLA diet (1% CLA w/w); or CLA plus methylprednisolone. Body composition, bone mineral content (BMC), and BMD were assessed with dual-energy X-ray absorptiometry at the onset and at the end of the 8-week intervention. The mechanical properties of bone were determined using 3-point femur bending at the end of the intervention. Methylprednisolone resulted in an attenuation of the increase in body mass and lean mass over the 8 weeks (p < 0.05). CLA prevented the methylprednisolone-induced attenuation of body mass and lean mass accumulation. CLA also resulted in a greater increase in BMC (p < 0.05) in the lumbar spine. The energy at failure of the isolated femurs was increased with CLA (p < 0.05). Dietary CLA prevents many of the growth- and bone-related side effects arising from 8 weeks of corticosteroid administration, results in greater increases in BMC and BMD, and can contribute to an improvement in some of the mechanical properties of bone.
Roy BD, Bourgeois J, Rodriguez C, Payne E…
Appl Physiol Nutr Metab Dec 2008
Effects of conjugated linoleic acid supplementation during resistance training on body composition, bone density, strength, and selected hematological markers.
Conjugated linoleic acids (CLA) are essential fatty acids that have been reported in animal studies to decrease catabolism, promote fat loss, increase bone density, enhance immunity, and serve as an antiatherogenic and anticarcinogenic agent. For this reason, CLA has been marketed as a supplement to promote weight loss and general health. CLA has also been heavily marketed to resistance-trained athletes as a supplement that may help lessen catabolism, decrease body fat, and promote greater gains in strength and muscle mass during training. Although basic research is promising, few studies have examined whether CLA supplementation during training enhances training adaptations and/or affects markers of health. This study evaluated whether CLA supplementation during resistance training affects body composition, strength, and/or general markers of catabolism and immunity. In a double-blind and randomized manner, 23 experienced, resistance-trained subjects were matched according to body mass and training volume and randomly assigned to supplement their diet with 9 g;pdd(-1) of an olive oil placebo or 6 g;pdd(-1) of CLA with 3 g;pdd(-1) of fatty acids for 28 days. Prior to and following supplementation, fasting blood samples, total body mass, and dual-energy X-ray absorptiometry (DEXA) determined body composition, and isotonic bench press and leg press 1 repetition maximums (1RMs) were determined. Results revealed that although some statistical trends were observed with moderate to large effect sizes, CLA supplementation did not significantly affect (p > 0.05) changes in total body mass, fat-free mass, fat mass, percent body fat, bone mass, strength, serum substrates, or general markers of catabolism and immunity during training. These findings indicate that CLA does not appear to possess significant ergogenic value for experienced resistance-trained athletes.
Kreider RB, Ferreira MP, Greenwood M, Wilson M…
J Strength Cond Res Aug 2002