The omega-6 arachidonic fatty acid, but not the omega-3 fatty acids, inhibits osteoblastogenesis and induces adipogenesis of human mesenchymal stem cells: potential implication in osteoporosis

Casado-Díaz, Antonio; Santiago-Mora, Raquel; Dorado, Gabriel; Quesada‐Gómez, José Manuel

doi:10.1007/s00198-012-2138-z

Cited by 93 publications

(78 citation statements)

References 40 publications

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“…We have previously reported that the AA favors the MSC differentiation into adipocytes (Casado-Diaz et al 2013), demonstrating that both 20 and 40 lM of AA enhance the adipogenesis, with a 40 lM concentration even inhibiting the osteoblastogenesis. We have further studied the 20 lM concentration in the present work, since when the AA is added with DHA or EPA to the culture medium, the PUFA concentration in the medium reaches 40 lM.…”

Section: Discussionmentioning

confidence: 89%

“…The MSC were isolated and cryopreserved as we have previously reported (Casado-Diaz et al 2013). The experiments were performed with a pool of cells obtained from such three donors.…”

Section: Bone Marrow Cell Culturesmentioning

confidence: 99%

“…On the other hand, fatty acids play a central role in the induction of mesenchymal stromal cells (MSC) to adipocyte differentiation, as well as in adipose tissue hypertrophy, because they have the ability to activate the peroxisome proliferator-activated receptor gamma (PPARc), which is a transcription factor inducing adipogenesis (Lopez et al 2003;Shillabeer and Lau 1994). We have previously shown that AA promotes a greater degree of adipocyte differentiation of MSC than DHA or EPA (Casado-Diaz et al 2013). Thus, not only the quantity of ingested fats, but also the nature of their fatty acid residues is of pivotal importance for human health.…”

Section: Introductionmentioning

confidence: 98%

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Effects of arachidonic acid on the concentration of hydroxyeicosatetraenoic acids in culture media of mesenchymal stromal cells differentiating into adipocytes or osteoblasts

et al. 2013

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Metabolites derived from the polyunsaturated fatty acids (PUFA) may modulate the mesenchymal stromal cell (MSC) differentiation. Such cells can differentiate into different cellular types, including adipocytes and osteoblasts. Aging favors the bone marrow MSC differentiation toward the former, causing a loss of bone density associated with pathologies like osteoporosis. The omega-6 arachidonic acid (AA) favors MSC adipogenesis to a greater extent than omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In this work, we study the joint action of both PUFA. Thus, not induced and induced to adipocyte or osteoblast MSC were treated with 20 lM of each PUFA (either AA, AA ? DHA or AA ? EPA). The expression of osteogenic and adipogenic molecular markers, the alox15b lipoxygenase gene expression and the 5-, 8-, 11-, 12-and 15-hydroxyeicosatetraenoic acids (HETE) derived from the AA metabolism in the culture media were determined. The results show that the adipogenesis induction of AA is not suppressed by the joint presence of EPA and DHA. In fact, both increased the adipogenic effect of AA on MSC differentiated into osteoblasts. The different HETE concentrations increased in cultures supplemented with AA, albeit such concentrations were lower in the cultures induced to differentiate, mainly at day 21 after the induction. Furthermore, the reduction in the HETE concentration was correlated with a higher expression of the alox15b gene. These results highlight the PUFA metabolism differences between uninduced and induced MSC to differentiate into adipocytes and osteoblasts, besides the relevant role of the lipoxygenase gene expression in adipogenesis induction.

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Section: Discussionmentioning

confidence: 89%

“…The MSC were isolated and cryopreserved as we have previously reported (Casado-Diaz et al 2013). The experiments were performed with a pool of cells obtained from such three donors.…”

Section: Bone Marrow Cell Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Effects of arachidonic acid on the concentration of hydroxyeicosatetraenoic acids in culture media of mesenchymal stromal cells differentiating into adipocytes or osteoblasts

et al. 2013

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“…Both n-6 and n-3 PUFA are ligands for PPARγ2, a transcription factor that activates adipogenic genes. In cultured human MSC stimulated to differentiate into adipocytes or osteoblasts, DHA treatment had no effect on adipogenesis, but a small effect on stimulating osteoblast differentiation [47]. Addition of EPA and DHA increased markers of mineralization, and thus stimulated the differentiation of MSCs to osteoblasts.…”

Section: Mechanisms Of Pufa In Bone Metabolismmentioning

confidence: 92%

“…It was shown that DHASCO feeding of young weanling rats (3 weeks) increased bone marrow cellularity [46]. Bone marrow contains mesenchymal stem cells (MSCs) that have the potential to differentiate into adipocytes or osteoblasts [47]. Therefore, depending on the developmental fate of MSC, these cells can either contribute to bone marrow adiposity by undergoing adipogenesis, or increase bone mass or BMD by increasing osteoblastogenesis.…”

Section: Mechanisms Of Pufa In Bone Metabolismmentioning

confidence: 99%

Investigating the Role of Polyunsaturated Fatty Acids in Bone Development Using Animal Models

et al. 2013

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Incorporating n-3 polyunsaturated fatty acids (PUFA) in the diet may promote the development of a healthy skeleton and thereby reduce the risk of developing osteoporosis in later life. Studies using developing animal models suggest lowering dietary n-6 PUFA and increasing n-3 PUFA intakes, especially long chain n-3 PUFA, may be beneficial for achieving higher bone mineral content, density and stronger bones. To date, the evidence regarding the effects of α-linolenic acid (ALA) remain equivocal, in contrast to evidence from the longer chain products, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This review reports the results of investigations into n-3 PUFA supplementation on bone fatty acid composition, strength and mineral content in developing animal models as well as the mechanistic relationships of PUFA and bone, and identifies critical areas for future research. Overall, this review supports a probable role for essential (ALA) and long chain (EPA and DHA) n-3 PUFA for bone health. Understanding the role of PUFA in optimizing bone health may lead to dietary strategies that promote bone development and maintenance of a healthy skeleton.

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Arachidonic acid metabolism in health and disease

Zhang,

Liu,

Sun

et al. 2023

MedComm

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Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

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The omega-6 arachidonic fatty acid, but not the omega-3 fatty acids, inhibits osteoblastogenesis and induces adipogenesis of human mesenchymal stem cells: potential implication in osteoporosis

Cited by 93 publications

References 40 publications

Effects of arachidonic acid on the concentration of hydroxyeicosatetraenoic acids in culture media of mesenchymal stromal cells differentiating into adipocytes or osteoblasts

Effects of arachidonic acid on the concentration of hydroxyeicosatetraenoic acids in culture media of mesenchymal stromal cells differentiating into adipocytes or osteoblasts

Investigating the Role of Polyunsaturated Fatty Acids in Bone Development Using Animal Models

Arachidonic acid metabolism in health and disease

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