http://www.jacn.org/cgi/content/full/19/4/478S
ABSTRACT
Conjugated Linoleic Acid and Bone Biology
Bruce A. Watkins, PhD, FACN and Mark F. Seifert, PhD
Purdue University, Department of Food Science, Lipid Chemistry and Molecular Biology Laboratory, West Lafayette, Indiana, and Department of Anatomy, Indiana University School of Medicine, Indianapolis, Indiana
Address reprint requests to: Dr. B.A. Watkins, Department of Food Science, Lipid Chemistry and Molecular Biology Laboratory, Purdue University, W. Lafayette, IN, 47907. E-mail:
watkins@foodsci.purdue.edu.
Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and induce cartilage degradation for which part of the response is mediated by PGE2. Excess production of PGE2 is linked to osteoporosis and arthritis and is associated with bone and proteoglycan loss. PGE2 also influences the IGF-I/IGFBP axis to facilitate bone and cartilage formation. Recent investigations with growing rats given butter fat and supplements of CLA demonstrated an increased rate of bone formation and reduced ex vivo bone PGE2 production, respectively...............
Anti-inflammatory diets, including nutraceutical n-3 fatty acids, are associated with decreased pathogenesis of rheumatoid arthritis (secondary osteoporosis), reduced inflammatory diseases [66–68] and lowered cancer risk [69]. The common link between these diseases resides in the regulation/expression of COX-2. For example, multiple lines of evidence indicate that up-regulation of COX-2 contributes to tumorigenesis and inflammation, providing tissue levels of prostanoid precursors that influence formation of the pro-inflammatory PGE2. In addition, chronic aspirin users (COX inhibitor) have reduced incidence of colorectal cancer. Both COX-1 and COX-2 inhibitors suppress experimental mouse skin carcinogenesis, and permanent overactivation of arachidonic acid metabolism appears to be a driving force for tumor development [70]. Moreover, metastasis of cancer to bone is a frequent outcome of breast (about two-thirds of patients with metastatic breast cancer have bone involvement) and prostate malignancies. The metastasis is often associated with significant morbidity (severe bone pain and pathologic fractures) due to osteolysis, and metastatic target bone is continually being remodeled under the influence of factors produced locally and systemically [71].
Interestingly, recent investigations suggest that both COX-2 induction and an increase in the supply of arachidonic acid are needed to greatly increase prostanoid production [72]. Supplying arachidonic acid appears to increase prostanoids to reduce the effects of nonsteroidal anti-inflammatory drugs, including NS-398 a specific COX-2 inhibitor. Therefore, in our view, n-3 fatty acids and CLA isomers may act as potent anticancer nutrients because they not only directly/indirectly affect the activity and expression of COX-2, but may also reduce the supply of arachidonic acid to diminish prostanoid biosynthesis. In any case, one mode of action for CLA appears to be anti-inflammatory with respect to reducing PGE2 production.
The data presented in this review describe consistent and reproducible effects of CLA isomers on decreasing ex vivo PGE2 production in bone organ cultures [33,34] and in various cell culture systems [51]. The potent beneficial anticancer effect of CLA is likely linked, in part, to down-regulation of COX-2 activity. Future investigations on CLA should evaluate isomeric effects on COX-1 and COX-2, for which over-expression of the latter is associated with carcinogenesis and inflammation. This research would lead to 1) important discoveries for bone modeling and remodeling, 2) development of delivery systems in designed/functional foods and 3) opportunities to identify a synergism between nutraceuticals and drug therapies to reduce cancer risk and control inflammatory bone/joint disease.
Hybrid Mode
