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Department of Food Science, Lipid Chemistry and Molecular Biology Laboratory, Purdue University, West Lafayette, IN 47907;
*
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523;
Department of Veterinary Medicine, University of Illinois, College of Veterinary Medicine, Urbana, IL 61801; and
**
Department of Anatomy, School of Medicine, Indiana University Purdue University, Indianapolis, IN 46202
3To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • polyunsaturated fatty acids • prostaglandin E2 • bone formation rate • alkaline phosphatase • rats
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). Both bone formation and bone resorption are influenced
by PGE2, and its effect on bone may be
concentration dependent. Raisz and Koolemans-Beynen (1974)
showed that PGE2 inhibits bone
matrix formation at high concentrations in bone organ culture; however,
at lower doses, PGE2 can stimulate bone formation
in vitro and in vivo (Chyun and Raisz 1984
, Jee et al. 1990
, Mori et al. 1990
, Raisz and Fall 1990
).
Watkins et al. (1996)
reported that an increased
production of bone PGE2 in tibia of chicks given
a semipurified diet containing soybean oil, high in (n-6)
polyunsaturated fatty acids (PUFA), was associated with a lower rate of
bone formation compared with that of chicks fed a low dietary ratio of
(n-6)/(n-3) fatty acids. Furthermore, dietary (n-3) PUFA were reported
to lower the concentration of AA in bone (Watkins et al. 1996
) and cartilage (Xu et al. 1994
), and
depress ex vivo PGE2 production in bone organ
culture. One explanation for this phenomenon in bone is that dietary
sources of PUFA that elevate AA cause an overproduction of
PGE2 in bone that leads to a reduced bone
formation rate. We hypothesize that the dietary ratio of (n-6)/(n-3)
fatty acids modulates bone PGE2 production to
influence other localized growth factors and protein biosynthesis in
osteoblasts responsible for bone formation.
Dietary lipids are known to affect the fatty acid composition of
membrane phospholipids to influence cell function. Investigators have
shown that lowering the dietary ratio of (n-6)/(n-3) fatty acids
resulted in increased bone marrow cellularity (Atkinson et al. 1997
) and bone strength (Kokkinos et al. 1993
).
Watkins et al. (1996)
reported that chicks fed a blend
of menhaden oil plus safflower oil in a semipurified diet had a lower
concentration of AA, but higher concentrations of 20:5(n-3) and
22:6(n-3) in cortical bone polar lipids compared with those fed soybean
oil. Moreover, reports by Alam et al. (1993)
in rat
alveolar bone and Xu et al. (1994)
in chicken cartilage
corroborate our findings that dietary PUFA alter the fatty acid
composition and PGE2 production in these tissues.
Dietary (n-3) fatty acids offer benefits by reducing the incidence and
severity of inflammatory disorders, cardiovascular diseases and some
cancers in humans (Rose 1997
, Suchner and Senftleben 1994
). Populations consuming fish, rich in (n-3)
fatty acids, have a low incidence of atherosclerotic disorders
(Goto et al. 1993
). Dietary fish oil, which is high in
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), also was
shown to reduce myocardial ischemic damage (Hock et al. 1997) and ventricular fibrillation (Billman et al. 1997
). The antitumorigenic effect of (n-3) fatty acids was
demonstrated in breast cancer (Braden and Carroll 1986
),
colon cancer (Minoura et al. 1988
, Reddy and Maruyama 1986
, Reddy and Sugie 1988
), and
pancreatic neoplasm (O’Connor et al. 1989
). The action
of (n-3) fatty acids is mediated in part by decreasing the production
of PGE2 and perhaps by down-regulating
cyclooxygenase-2 (COX-2) activity (Hamilton et al. 1999
)
in local tissues. Because the prostanoid PGE2
plays an important role in bone metabolism, we speculate that by
modulating the dietary ratio of (n-6)/(n-3) fatty acids, bone growth
could be optimized during bone modeling.
To our knowledge, there is no investigation evaluating how the dietary ratio of (n-6)/(n-3) fatty acids affects tissue PGE2 production and bone formation in growing animals. The aim of this study was threefold: 1) to investigate how the dietary ratio of (n-6)/(n-3) fatty acids influences the fatty acid composition of bone compartments; 2) to determine correlations between bone fatty acid composition and ex vivo bone PGE2 production; and 3) to identify, using regression analysis, the relationship between bone PGE2 concentration and the rate of bone formation.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Male weanling rats (n = 60; 21-d-old, mean body
weight 45.4 ± 3.3 g, Harlan Sprague Dawley, Indianapolis,
IN) were housed in individual cages at a controlled temperature of
21–23°C with a 12-h light:dark cycle. Animal care was in compliance
with applicable guidelines from the Purdue University policy on animal
care and use. The rats were assigned randomly to four groups and
consumed ad libitum the basal diet (AIN-93G without fat, Dyets,
Bethlehem, PA) with one of the fat treatments (Table 1
). The dietary treatments were prepared by mixing safflower oil and
menhaden oil at different proportions (SMI, 90:10; SMII, 80:20; SMIII,
50:50; and SMIV, 30:70; wt/wt). The dietary lipid treatments were
formulated to provide linoleic acid 18:2(n-6) at 24–67 g/100 g fatty
acids and contain increasing amounts of 20:5(n-3) EPA and 22:6(n-3)
DHA. Total fat concentration in each diet was 70 g/kg. All dietary
lipids were stored at -80°C before use. Fresh diets were mixed every
14 d and all diets were kept at -20°C until fed. Food cups were
refilled three times each week. Food consumption was measured at the
time when the food cup was refilled. Body weights were recorded weekly
and feed efficiencies (total g weight gain/total g food consumed)
calculated for each treatment group.
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After 42 d of dietary treatment, the rats were killed and tissue
samples (blood, liver and right femur) collected for lipid analysis.
Blood was collected from axillary vessels. Serum was separated by
centrifuging the clotted blood at 1200 x g for 20
min and storing the blood at -80°C until analyzed. For dynamic
assessment of bone formation rate, rats were given double
intraperitoneal injections of calcein green (10 mg/kg body weight,
Sigma Chemical, St. Louis, MO) 6 and 2 d before killing (Li et al. 1999
, Watkins et al. 1996
). All samples
were kept on ice at the time of collection and then frozen at -80°C.
Bones were removed and carefully freed of soft tissue. Right proximal
tibiae, collected for bone histology, were fixed in 10% neutral
buffered formalin, dehydrated in ethanol and embedded undecalcified in
methylmethacrylate (Seifert 1994
, Watkins et al. 1996
).
Analytical procedures.
Lipids in the diet and tissue samples were extracted with
chloroform/methanol (2:1, v/v). Cortical bone samples were cooled in
liquid nitrogen, pulverized and sonicated for extraction of lipids
(Watkins et al. 1996
). Total lipids extracted were
further separated into polar and neutral lipid fractions by solid phase
extraction (Juaneda and Rocquelin 1985
) using silica
(600-mg) cartridges (Alltech Maxi-clean, Alltech, Deerfield, IL).
Lipids from the diet and rat tissues were saponified, and fatty acid methyl esters (FAME) prepared by esterification using boron trifluoride (BF3) in methanol (14%, wt/wt, Supelco Bellefonte, PA). FAME were analyzed using a gas chromatograph (GC HP 5890 series II, autosampler 7673, HP 3365 ChemStation; Hewlett-Packard, Avondale, PA) equipped with a DB 23 column (30 m, 0.53 mm i.d., 0.5 µm film thickness; J&W Scientific, Folsom, CA). The GC was operated at 140°C for 2 min, temperature programmed 1.5°C/min to 198°C and held for 7 min. The injector and flame-ionization detector temperatures were 225 and 250°C, respectively. FAME were identified by comparison of retention times with authentic standards (GLC-422, GLC-87, GLC-68A, Nu-Chek-Prep, Elysian, MN) and FAME prepared from menhaden oil (Matreya, Pleasant Gap, PA).
Bone histomorphometric analyses were performed on frontal sections of
proximal tibial metaphyses cut using a Reichert-Jung 2050 microtome
(Nussloch, Germany). Kinetic measurements were performed on unstained
sections (10 µm thick) viewed using fluorescence
microscopy (Seifert 1994
, Watkins et al. 1996
). Trabecular tissues were measured in a standard area (2.4
mm2) located just below the growth plate zone of
mineralized cartilage, composed of secondary spongiosae. This area
excluded trabeculae connected to the osseous cortex. Two sections per
rat were analyzed at an objective magnification of X20, and kinetic
parameters (double labels located along endocortical surfaces) were
measured in the same area. Sections were analyzed using a semiautomatic
image analysis system (Osteomeasure Histomorphometry System,
Osteometrics, Atlanta, GA) (Seifert 1994
). Kinetic
parameters were measured from unstained sections for bone formation
rate (BFR)/bone surface (µm/d). This measurement is an
indicator of bone formation, and the formula used for the calculation
is based on the recommendations of the American Society for Bone and
Mineral Research Nomenclature Committee (Parfitt et al. 1987
).
Ex vivo PGE2 production in liver homogenates and bone organ
cultures was determined by RIA as previously described (Li et al. 1999
, Watkins et al. 1996
and 1997
).
Briefly, 1 g of liver was homogenized in 10 mL of 50 mmol/L
potassium phosphate buffer (pH 7.4, 4°C), and the homogenates were
incubated in a shaking incubator for 10 min at 37°C. Incubation was
terminated with 0.5 volumes of acetylsalicylic acid (42 mmol/L). Liver
homogenates were stored at -80°C until analyzed for
PGE2. Shafts from the left tibia and femur bones were
removed and carefully flushed with 9 g/L NaCl to remove marrow cells. A
section of bone shaft was immersed in 20 mL of Hank’s balanced salt
solution (Sigma Chemical) and incubated with shaking for 2 h at
37°C. After incubation, the bone culture medium was collected and
stored at -80°C until analyzed. Values for PGE2 were
expressed per unit of cytosolic protein for liver homogenate and per
unit of bone wet or dry weight.
The activity of serum alkaline phosphatase isoenzymes (total,
intestinal, liver and bone-specific) was measured as previously
described (Hoffmann et al. 1994
, Solter et al. 1997
). Serum intact osteocalcin was measured by an
immunoradiometric assay using a commercial kit (Immutopics, San
Clemente, CA).
Statistical analysis.
Data were analyzed by one-way ANOVA; when significant differences were found, a Student-Newman-Keuls or Duncan’s Multiple Range Test was performed at a probability of P = 0.05. Correlations between selected measurements were tested by Pearson’s correlation analysis (SAS software package for UNIX, SAS Institute Cary, NC). A t test was also used to examine the differences in bone formation rates. Variations between treatment groups were expressed as the pooled standard error of the mean (SEM) or mean ± SEM where applicable.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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. The SMIV diet had the lowest value for the ratio of (n-6)/(n-3)
fatty acids and contained 12.6 g EPA and 4.6 g DHA/100 g
total fatty acids. The amount of 18:2(n-6) linoleic acid and 18:3(n-3)
-linolenic acid ranged from 24 to 68 g and 0.1 to 0.5 g/100 g
of the total fatty acids, respectively. Rat growth was not affected by the dietary lipid treatments (final body weight: SMI, 305.7 ± 4.2 g; SMII, 301.7 ± 5.0 g; SMIII, 308.3 ± 4.6 g; and SMIV, 306.7 ± 4.1 g). Feed efficiency also was not influenced by the dietary treatments (SMI, 0.41 ± 0.004; SMII, 0.40 ± 0.003; SMIII, 0.42 ± 0.009; and SMIV, 0.42 ± 0.004 g body weight gained/g food consumed).
The concentration of total (n-6) fatty acids, AA and 18:2(n-6) declined
according to the dietary ratio of (n-6)/(n-3) fatty acids in polar
lipids of periosteum (Table 2
), marrow (Table 3
) and cortical bone (Table 4
) in rats. The reduction in the total amount of (n-6) fatty acids was
30–50%, 29–50% for AA and 12–15% for 18:2(n-6) in rats fed a
dietary ratio of (n-6)/(n-3) fatty acids of 1.2 (SMIV) compared with
those fed an (n-6)/(n-3) ratio of 23.8 (SMI). Moreover, as the dietary
level of (n-3) fatty acids rose from 2.85 to 21.15%, the concentration
of total (n-3) fatty acids was elevated by 66–200%, and EPA by
800-1940% in rat periosteum, marrow and cortical bone polar lipids.
The concentration of DHA in periosteum was elevated but remained
unchanged in marrow and cortical bone of rats fed the SMIII and SMIV
diets containing higher levels of (n-3) fatty acids (Table 2)
. As the
dietary ratio of (n-6)/(n-3) fatty acids approached the lowest value
(1.2), the concentration of total monounsaturates rose and total
saturates remained unchanged in polar lipids of all femur bone
compartments in the rat. The ratio of AA/EPA in polar lipids ranged
from 2.3 to 39.3 in periosteum (Table 2)
, 3.0 to 62.5 in marrow (Table 3)
and 3.8 to 27.4 in cortical bone (Table 4)
of rats fed the different
dietary treatments.
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), marrow (Table 6
) and cortical bone (Table 7
). The neutral lipids of all bone compartments of rats fed the highest
level of dietary (n-3) fatty acids contained from 2.9- to 5.6-fold
greater concentrations of total (n-3), 9- to 14.5-fold for EPA and 1.8
to 4-fold for DHA compared with those fed the lowest level of (n-3). In
rats fed the SMIV diet [highest level of (n-3) fatty acids], the
total concentration of saturates and monounsaturates was elevated in
neutral lipids of periosteum and marrow compared with rats fed the SMI
diet. In all bone compartments, the total concentration of PUFA in
neutral lipids was lower in rats fed the SMIV diet.
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. The concentration of AA in g/100 g found in polar lipids of periosteum (7.6–14.5), marrow (11.9–20.4) and cortical bone (9.2–13.4) was greater than that in the neutral lipids of those respective bone compartments (0.9–1.9, 2.0–3.2, 2.0–5.3). In addition, these data showed that as the dietary ratio of (n-6)/(n-3) fatty acids approached 1.2, the increase in concentration of EPA in polar lipids was greater than the drop in concentration of AA in rat bone compartments. For example, the concentration of AA in polar lipids was reduced by only 29 to 48%, whereas that for EPA rose from 9- to 24-fold in rats fed a lower dietary ratio of (n-6)/(n-3) fatty acids.
Measurement of ex vivo PGE2 production in bone
and serum biomarkers of bone formation showed that as the dietary ratio
of (n-6)/(n-3) fatty acids declined from 23.9, more favorable
conditions resulted, which tended to reflect improved bone modeling in
growing rats (Table 8
). The amount of ex vivo PGE2 produced in liver
homogenates and bone organ cultures across the treatment groups closely
followed the changes in concentrations of AA and EPA in bone tissue
polar lipids. Ex vivo PGE2 production in femur
and tibia was 43–55% lower in rats fed a higher amount of (n-3) fatty
acids in the SMIV diet compared with the values in rats fed the SMI
diet. These results were consistent with liver homogenate prostanoid
production from rats fed the experimental diets (Table 8)
. The
activities of serum alkaline phosphatase (ALP) isoenzymes were
significantly higher in rats fed the higher levels of dietary (n-3)
fatty acids compared with those fed the highest level of (n-6) in the
SMI diet (Table 8)
. The activities for total ALP (TALP), intestinal ALP
(IALP), liver ALP (LALP), and bone ALP (BALP), rose progressively with
the decline in the dietary ratio of (n-6)/(n-3) fatty acids. In this
study, serum intact osteocalcin was not affected by the dietary ratio
of (n-6)/(n-3) fatty acids after 6 wk of dietary treatment (Table 8)
.
However, there was a higher BFR in tibia of rats fed the greatest level
of (n-3) fatty acids in the SMIV diet compared with the rate in rats
fed the SMI diet [highest in (n-6) fatty acids] (Table 8)
.
|
, panel A). Furthermore, a significant negative correlation
was observed between BFR and the ratio of AA/EPA (Fig. 1
, panel
B) and with PGE2 (Fig. 1
, panel
C). The regression analyses suggest that bone concentrations of
(n-6) and (n-3) fatty acids are related to changes in ex vivo
PGE2 production and may be associated with an
altered rate of bone formation.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The lack of dietary treatment effect on serum osteocalcin in rats at 9
wk of age might be related to the time at which sampling was performed.
Modrowski et al. (1992)
found that the maximum levels of
this biomarker of bone formation are achieved at 3 wk and drop
precipitously through 11 wk of age. Moreover, it has been reported that
an osteocalcin surge precedes the period of rapid skeletal growth in
rats (Modrowski et al. 1992
). Values for serum
osteocalcin in the present study are consistent with those reported for
rats of a similar age. Therefore, on the basis of the current data, it
is possible to observe a difference in rate of bone formation without a
change in serum osteocalcin in growing rats.
The value for bone-specific ALP might be the best biomarker for
bone formation in this study. Its activity, as well as that of other
isoenzymes of alkaline phosphatase seems to be "coupled" to tissue
PGE2 concentration. Liver homogenate and bone
PGE2 levels declined in rats from the SMI to SMIV
groups, but activity of total ALP and its isoenzymes rose in these
tissues. This phenomenon seems to corroborate our previous findings in
growing chicks (Watkins et al. 1996
) in that those fed
(n-3) PUFA had higher circulating levels of ALP. The apparent
inhibitory effect of PGE2 on the activity of ALP
is consistent with the findings of Fujimori et al. (1989)
and Igarashi et al. (1994)
who reported
that acetylsalicylic acid added to cultured MC3T3-E1 cells resulted in
depressed endogenous PGE2 levels but elevated ALP
activity.
This investigation evaluated the effects of varying the dietary ratio of (n-6)/(n-3) fatty acids on bone tissues. The fatty acid composition of neutral and polar lipids in periosteum, marrow and cortical bone reflected the dietary levels of (n-6) and (n-3) fatty acids fed to rats. As the dietary levels of EPA and DHA rose, the concentration of AA declined in all lipids of the bone compartments studied. The concentrations of EPA in cortical bone, periosteum and marrow were negatively correlated (r = -0.82 to -0.86, P < 0.0001) and concentrations of AA positively correlated (r = 0.64–0.95, P < 0.002) with the dietary ratio of (n-6)/(n-3) fatty acids.
The dietary ratio of EPA to DHA was 
3.0 for the different lipid
treatments of (n-6)/(n-3) fatty acids. Hence, the absolute amount of
EPA was greater than that of DHA in the diets, and the treatments
resulted in significantly higher concentrations of EPA relative to DHA
in polar lipids of bone compartments. In contrast, the neutral lipids
contained nearly the same concentration of both fatty acids.
Alam et al. (1993)
reported similar concentrations
(4.2–4.7%) of both EPA and DHA in total phospholipids of mandibles
and maxillae of rats fed ethyl esters of EPA and DHA provided in a
dietary ratio of 1.35. These studies indicate that the proportion of
EPA and DHA influences the polar lipid composition of long-chain
(n-3) fatty acids but less so for neutral lipid in bone. Furthermore,
as dietary 18:2(n-6) was replaced with EPA and DHA, the concentration
of AA declined significantly in cortical bone, periosteum and marrow.
The correlations between the bone ratio of AA/EPA and ex vivo PGE2 production in bone and BFR revealed important associations. Although variables indicating high correlations do not demonstrate a cause-effect connection, a high correlation suggests that a relationship does exist. We clearly showed that dietary PUFA, specifically the ratio of (n-6)/(n-3) fatty acids, are a factor in determining bone tissue content of AA and EPA, and this in turn determines capacity to synthesize PGE2. It is possible that other eicosanoids are affected, and modulation of biosynthesis can exert a positive or negative influence on (patho-) physiologic events in bone.
PGE is involved in bone metabolism under both normal (Marks and Miller 1993
) and disease conditions (Kremer 1996
). In an in vitro human bone study, Plotquin et al. (1991)
showed that PGE production was 5–30 times higher in
osteomyelitic bone compared with normal controls. Moreover,
PGE2 production is involved in the inflammatory
condition and in the bone resorption that occurs in osteomyelitis.
Production of PGE2 by COX-2, an inducible enzyme,
is stimulated by cytokines in adult human osteoblast-like cells
(Xu et al. 1997
). In human osteoblast cell cultures,
parathyroid hormone induced COX-2 expression and
PGE2 production (Maciel et al. 1997
); in rats, COX-2 induction is important for lamellar bone
formation elicited by mechanical strain (Forwood 1996
).
Overexpression of COX-2 is associated with inflammatory response in
arthritis and in the development of osteoporosis and cancer
(Subbaramaiah et al. 1997
). Each year, $70 billion is
spent to treat patients suffering from osteoporosis, and arthritis
afflicts 40 million people in the U.S. (Lawrence et al. 1998
).
Inflammatory cytokines (e.g., interleukin-1) are known to inhibit
chondrocyte proliferation (Arend and Dayer 1990
) and
induce cartilage degradation; part of that response is mediated by
PGE2 (Fukuda et al. 1994
). Excess
production of PGE2 is linked to joint pathology
(rheumatoid arthritis), is known to exacerbate inflammatory responses
and results in a net loss of proteoglycan from articular cartilage
(Fukuda et al. 1994
). Because PGE2
activation of the insulin-like growth factor (IGF)-I/IGF binding
protein axis may play an important role in cartilage biology, (e.g.,
collagen and proteoglycan synthesis) (Di Battista et al. 1997
), dietary fatty acids may also be important for supporting
joint repair. Our investigation with rats demonstrates that the dietary
ratio of (n-6)/(n-3) fatty acids alters AA concentrations in bone
compartments and modulates PGE2 production and
other local factors affecting bone modeling.
Prostaglandin E3 (PGE3), an
eicosanoid derivative of EPA, could have increased in rats fed the high
(n-3) diet because the proportion of dietary EPA to DHA was 2.35–2.7
to 1, and this was reflected in the concentration of bone EPA relative
to DHA. PGE3 is as potent as
PGE2 in mediating bone resorption; however, EPA
is a less effective substrate for cyclooxygenase than AA (Raisz et al. 1989
). Hence, supplementation with oils providing
appreciable amounts of EPA typically reduces the 2-series PG derived
from AA, accompanied by a small increase in 3-series PG derived from
EPA (Knapp et al. 1986
). Because
PGE3 is less inflammatory than
PGE2 (Kremer 1996
), a possible
mechanism for the effect of a high (n-3) fatty acid intake on bone
formation (or alternatively, changes in bone resorption) could be
attributed to reductions in bone resorbing PGE2
accompanied by small increases in PGE3. In
addition, the response could also be due to reduced AA concentration in
phospholipids attributable to increased EPA.
Croft et al. (1988)
reported an antagonistic effect of
EPA on AA in leukocytes from rats fed an EPA-rich fish oil diet. In
the study on leukocytes, EPA caused a decrease in leukotriene
B4 (LTB4) and thromboxane
B2 (TxB2) production but an
increase in leukotriene B5
(LTB5), a lipoxygenase product of EPA. The
bioactivity of LTB5 is less than that of
LTB4 (Miller et al. 1993
). For the
present study, the reduction in ex vivo PGE2
production in rat bone is most likely not related to tissue DHA levels
as evidenced by the fact that the relative amount of DHA in polar
lipids was less than that for EPA. EPA and DHA may have distinct
functions in regulation of eicosanoid production for bone metabolism.
It has been shown that EPA but not DHA altered platelet prostaglandin
biosynthesis in rats (Bruckner et al. 1984
), which
further supports a more important role for EPA in the regulation of
PGE2 biosynthesis.
Anti-inflammatory diets, including nutraceutical (n-3) fatty acids,
attenuate symptoms of rheumatoid arthritis (secondary osteoporosis),
certain inflammatory diseases (Geusens et al. 1994
,
Kremer 1996
, Shapiro et al. 1996
) and
cancer risk (Rose 1997
). These beneficial effects of
(n-3) fatty acids were demonstrated in a mouse model for arthritis
(Leslie et al. 1985
). For example, a longer time period
was observed before induction of the disease in mice fed a fish oil
diet compared with those fed corn oil, which is high in 18:2(n-6). In
addition, these mice showed a decreased incidence and severity of their arthritis (Leslie et al. 1985
). A common link
between osteoarthritis (bone loss) and rheumatoid arthritis,
and conditions for optimizing bone formation resides in the
regulation/expression of COX-2. In this study, our findings support a
positive role for (n-3) fatty acids in bone modeling in growing rats
and provide a therapeutic context for the use of dietary (n-3) fatty
acids in modulating eicosanoid production to control bone disease.
Research on nutraceutical fatty acids is now directed toward
investigations to evaluate effects on the activity and expression of
COX-2 in MC3T3-E1 cells and rats.
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FOOTNOTES |
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2 Supported by grant no. 96–35200-3137 from the U.S. Department of Agriculture N.R.I.
4 Abbreviations used: AA, arachidonic acid; ALP, alkaline phosphatase; BF3, boron trifluoride; BFR, bone formation rate; COX-2, cyclooxygenase-2; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FAME, fatty acid methyl esters; GC, gas chromatograph; IGF, insulin-like growth factor; LTB4, leukotriene B4; LTB5, leukotriene B5; PGE2, prostaglandin E2; PGE3, prostaglandin E3; PUFA, polyunsaturated fatty acids; SMI, II, III, IV, sunflower oil/menhaden oil diets; TxB2, thromboxane B2.
Manuscript received November 18, 1999. Initial review completed January 11, 2000. Revision accepted April 6, 2000.
|
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|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
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