Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis

Md Mizanur Rahman, Gabriel Fernandes, Paul Williams

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight-week old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5 % safflower oil (SFO) or 0.5 % CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/Ovx and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO-fed mice. Reverse transcriptase polymerase chain reaction and fluorescence activated cell sorting analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic receptor activator of NF-κB (RANKL) and stimulated decoy receptor of RANKL, osteoprotegerin expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of lipopolysaccharide-stimulated splenocytes and BM cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by tartrate resistant acid phosphatase and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss.

Original languageEnglish (US)
Pages (from-to)211-224
Number of pages14
JournalLipids
Volume49
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Conjugated Linoleic Acids
Ovariectomy
Osteogenesis
Bone
Bone and Bones
Safflower Oil
Bone Density
Postmenopausal Osteoporosis
Bone Resorption
lissamine rhodamine B
Minerals
Bone Marrow Cells
Estrogens
Cytokines
Osteoprotegerin
Cells
Osteoclasts
Complementary Therapies
Thigh
Reverse Transcriptase Polymerase Chain Reaction

Keywords

  • Bone mineral density
  • Inflammation
  • Osteoblastogenesis
  • Osteoclastogenesis
  • Osteoporosis
  • Ovariectomy

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Organic Chemistry

Cite this

Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis. / Rahman, Md Mizanur; Fernandes, Gabriel; Williams, Paul.

In: Lipids, Vol. 49, No. 3, 2014, p. 211-224.

Research output: Contribution to journalArticle

Rahman, Md Mizanur ; Fernandes, Gabriel ; Williams, Paul. / Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis. In: Lipids. 2014 ; Vol. 49, No. 3. pp. 211-224.
@article{3c8c77a9fbee44ffb7a03183be3d4cf1,
title = "Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis",
abstract = "Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight-week old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5 {\%} safflower oil (SFO) or 0.5 {\%} CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/Ovx and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO-fed mice. Reverse transcriptase polymerase chain reaction and fluorescence activated cell sorting analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic receptor activator of NF-κB (RANKL) and stimulated decoy receptor of RANKL, osteoprotegerin expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of lipopolysaccharide-stimulated splenocytes and BM cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by tartrate resistant acid phosphatase and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss.",
keywords = "Bone mineral density, Inflammation, Osteoblastogenesis, Osteoclastogenesis, Osteoporosis, Ovariectomy",
author = "Rahman, {Md Mizanur} and Gabriel Fernandes and Paul Williams",
year = "2014",
doi = "10.1007/s11745-013-3872-5",
language = "English (US)",
volume = "49",
pages = "211--224",
journal = "Lipids",
issn = "0024-4201",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis

AU - Rahman, Md Mizanur

AU - Fernandes, Gabriel

AU - Williams, Paul

PY - 2014

Y1 - 2014

N2 - Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight-week old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5 % safflower oil (SFO) or 0.5 % CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/Ovx and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO-fed mice. Reverse transcriptase polymerase chain reaction and fluorescence activated cell sorting analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic receptor activator of NF-κB (RANKL) and stimulated decoy receptor of RANKL, osteoprotegerin expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of lipopolysaccharide-stimulated splenocytes and BM cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by tartrate resistant acid phosphatase and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss.

AB - Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight-week old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5 % safflower oil (SFO) or 0.5 % CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/Ovx and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO-fed mice. Reverse transcriptase polymerase chain reaction and fluorescence activated cell sorting analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic receptor activator of NF-κB (RANKL) and stimulated decoy receptor of RANKL, osteoprotegerin expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of lipopolysaccharide-stimulated splenocytes and BM cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by tartrate resistant acid phosphatase and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss.

KW - Bone mineral density

KW - Inflammation

KW - Osteoblastogenesis

KW - Osteoclastogenesis

KW - Osteoporosis

KW - Ovariectomy

UR - http://www.scopus.com/inward/record.url?scp=84895873318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895873318&partnerID=8YFLogxK

U2 - 10.1007/s11745-013-3872-5

DO - 10.1007/s11745-013-3872-5

M3 - Article

C2 - 24338525

AN - SCOPUS:84895873318

VL - 49

SP - 211

EP - 224

JO - Lipids

JF - Lipids

SN - 0024-4201

IS - 3

ER -