Flaxseed oil ameliorated high-fat-diet-induced bone loss in rats by promoting osteoblastic function in rat primary osteoblasts

Chen, Fulian; Wang, Yan; Wang, Hongwei; Dong, Zhenhua; Zhang, Mengqi; Li, Jiaxuan; Shao, Shanshan; Yu, Chunxiao; Huan, Zhikun; Xu, Jianhua

doi:10.1186/s12986-019-0393-0

Cited by 33 publications

(21 citation statements)

References 44 publications

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“…The present study, as previously reported [2,23], validated that the deleterious skeletal changes were found in cancellous bone, but not in cortical bone of hyperlipidemia rats, which may be due to the compact and solid structure of cortical bone and the lower remodeling activity than that of honeycomb cancellous bone. An in vivo study demonstrated that hyperlipidemia signi cantly increased implant loss and decreased the formation of the bone-to-implant interface in the mouse femur [24].…”

Section: Discussionsupporting

confidence: 90%

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High-carbohydrate, High-fat Diet-induced Hyperlipidemia Hampers the Differentiation Balance of Bone Marrow Mesenchymal Stem Cells by Suppressing Autophagy via the AMPK/ mTOR Pathway in Rat Models

Shang

Zhang

Jiang

et al. 2020

Preprint

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Background: Disorders of bone metabolism caused by hyperlipidemia is not conducive to osseointegration of implants. Autophagy, an evolutionarily conserved, lysosomal-mediated degradation process, is indispensable for bone homeostasis, its effects on hyperlipidemia-induced osteoporosis remain to be elucidated. The objective of this study was to determine whether autophagy affects bone metabolism and implant osseointegration through regulating the function of bone marrow mesenchymal stem cells (BMMSCs) in rats with hyperlipidemia and to confirm signaling pathway involved in the regulation of autophagy. Methods: Hyperlipidemia models were established through a long-term high-carbohydrate, high-fat diet in 6-week-old male Sprague-Dawley rats. The impact of hyperlipidemia on bone metabolism and early osseointegration of implants was explored by the methods including serum biochemical detection, micro-computed tomography and bone morphology detection. Biological properties and autophagy levels of BMMSCs were also determined. Further, we determined if autophagy was involved in bone metabolism changes resulting from high-fat diet by focusing on the lineage differentiation of BMMSCs. The signaling pathway involved in the regulation of autophagy was also explored.Results: The high-carbohydrate, high-fat diet (HCHF) was given to the rats for seven months aggravated bone loss in the cancellous bone and reduced osseointegration of implants. BMMSCs from hyperlipidemia rats exhibited decreased osteogenesis, increased adipogenesis and decreased autophagic activity compared with regular diet (RD) BMMSCs. Rapamycin treatment restored the impaired osteogenic differentiation and inhibited the adipogenic differentiation of HCHF-BMMSCs through the activation of autophagy. Further, AMPK/mTOR signaling pathways was related to the impairment of autophagy of HCHF-BMMSCs. Conclusions: Our data indicate that long-term high-carbohydrate, high-fat diet-induced hyperlipidemia hampers the differentiation balance of bone marrow mesenchymal stem cells by suppressing autophagy via the AMPK/ mTOR pathway, which ultimately led to aggravated bone loss in the cancellous bone and reduced osseointegration of implants in rat models.

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Section: Discussionsupporting

confidence: 90%

“…Hyperlipidemia is a lipid abnormality characterized by elevated serum cholesterol and triglycerides. Multiple clinical and animal studies suggested that hyperlipidemia and osteoporosis were intimately interrelated [1][2][3]. Low bone mineral density (BMD) were found in postmenopausal women with high serum total cholesterol (TC).…”

Section: Introductionmentioning

confidence: 99%

High-carbohydrate, High-fat Diet-induced Hyperlipidemia Hampers the Differentiation Balance of Bone Marrow Mesenchymal Stem Cells by Suppressing Autophagy via the AMPK/ mTOR Pathway in Rat Models

Shang

Zhang

Jiang

et al. 2020

Preprint

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“…To identify potential epigenetic mediators of these effects, we performed targeted pyrosequencing for DNA methylation analysis of the promoters for the Bmpr1a, Ptch1, Sirt1, Osx, and Igf1r genes, while Runx‐2, Alp, Col1a1, and Bglap were only used as osteogenic markers. The expression patterns of these genes are known to be affected by diet 53‐57 . They are also considered as crucial molecular players in the major signaling pathways that control osteoblastic differentiation and activity: Bmpr1a in BMP pathway, Ptch1 in hedgehog pathway, Igf1r in IGF signaling, while Osx is a master regulator of osteoblast differentiation and Sirt1 links nutritional diet with bone formation 58 .…”

Section: Resultsmentioning

confidence: 99%

“…The expression patterns of these genes are known to be affected by diet. [53][54][55][56][57] They are also considered as crucial molecular players in the major signaling pathways that control osteoblastic differentiation and activity: Bmpr1a in BMP pathway, Ptch1 in hedgehog pathway, Igf1r in IGF signaling, while Osx is a master regulator of osteoblast differentiation and Sirt1 links nutritional diet with bone formation. 58 All the samples demonstrated negligible DNA methylation, consistent with the promoters being in the active state, with signal ranging within the established noise area of the technology.…”

Section: Dna Methylation Analysismentioning

confidence: 99%

Low protein intake during reproduction compromises the recovery of lactation‐induced bone loss in female mouse dams without affecting skeletal muscles

et al. 2020

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Lactation‐induced bone loss occurs due to high calcium requirements for fetal growth but skeletal recovery is normally achieved promptly postweaning. Dietary protein is vital for fetus and mother but the effects of protein undernutrition on the maternal skeleton and skeletal muscles are largely unknown. We used mouse dams fed with normal (N, 20%) or low (L, 8%) protein diet during gestation and lactation and maintained on the same diets (NN, LL) or switched from low to normal (LN) during a 28 d skeletal restoration period post lactation. Skeletal muscle morphology and neuromuscular junction integrity was not different between any of the groups. However, dams fed the low protein diet showed extensive bone loss by the end of lactation, followed by full skeletal recovery in NN dams, partial recovery in LN and poor bone recovery in LL dams. Primary osteoblasts from low protein diet fed mice showed decreased in vitro bone formation and decreased osteogenic marker gene expression; promoter methylation analysis by pyrosequencing showed no differences in Bmpr1a, Ptch1, Sirt1, Osx, and Igf1r osteoregulators, while miR‐26a, ‐34a, and ‐125b expression was found altered in low protein fed mice. Therefore, normal protein diet is indispensable for maternal musculoskeletal health during the reproductive period.

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“…To identify potential epigenetic mediators of these effects, we performed targeted pyrosequencing for DNA methylation analysis of the promoters for the Bmpr1a, Ptch1, Sirt1, Osx and Igf1r genes, while Runx-2, Alp, Col1a1 were only used as osteogenic markers. The expression patterns of these genes are known to be affected by diet (53)(54)(55)(56)(57). They are also considered as crucial molecular players in the major signaling pathways that control osteoblastic differentiation and activity: Bmpr1a in BMP pathway, Ptch1 in hedgehog pathway, Igf1r in IGF signaling, while Osx is a master regulator of osteoblast differentiation and Sirt1 links nutritional diet with bone formation (58).…”

Section: Dna Methylation Analysismentioning

confidence: 99%

Low protein intake compromises the recovery of lactation-induced bone loss in female mouse dams without affecting skeletal muscles

Kanakis

Alameddine

Scalabrin

et al. 2020

Preprint

View full text Add to dashboard Cite

Lactation-induced bone loss occurs due to high calcium requirements for fetal growth but skeletal recovery is normally achieved promptly post-weaning. Dietary protein is vital for fetus and mother but the effects of protein undernutrition on the maternal skeleton and skeletal muscles is largely unknown. We used mouse dams fed with normal (N, 20%) or low (L, 8%) protein diet during gestation and lactation and maintained on the same diets (NN, LL) or switched from low to normal (LN) during a 28d skeletal restoration period post lactation. Skeletal muscle morphology and neuromuscular junction integrity was not different between any of the groups. However, dams fed the low protein diet showed extensive bone loss by the end of lactation, followed by full skeletal recovery in NN dams, partial recovery in LN and poor bone recovery in LL dams. Primary osteoblasts from low protein diet fed mice showed decreased in vitro bone formation and decreased osteogenic marker gene expression; promoter methylation analysis by pyrosequencing showed no differences in Bmpr1a, Ptch1, Sirt1, Osx and Igf1r osteoregulators, while miR-26a, -34a and -125b expression was found altered in low protein fed mice. Therefore, normal protein diet is indispensable for maternal musculoskeletal health during the reproductive period.

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Flaxseed oil ameliorated high-fat-diet-induced bone loss in rats by promoting osteoblastic function in rat primary osteoblasts

Cited by 33 publications

References 44 publications

High-carbohydrate, High-fat Diet-induced Hyperlipidemia Hampers the Differentiation Balance of Bone Marrow Mesenchymal Stem Cells by Suppressing Autophagy via the AMPK/ mTOR Pathway in Rat Models

High-carbohydrate, High-fat Diet-induced Hyperlipidemia Hampers the Differentiation Balance of Bone Marrow Mesenchymal Stem Cells by Suppressing Autophagy via the AMPK/ mTOR Pathway in Rat Models

Low protein intake during reproduction compromises the recovery of lactation‐induced bone loss in female mouse dams without affecting skeletal muscles

Low protein intake compromises the recovery of lactation-induced bone loss in female mouse dams without affecting skeletal muscles

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