Perturbations in the HDL metabolic pathway predispose to the development of osteoarthritis in mice following long-term exposure to western-type diet

Triantaphyllidou, Irene-Eva; Kalyvioti, Elena; Karavia, Eleni A.; Lilis, Ioannis; Kypreos, Kyriakos E.; Papachristou, Dionysios J.

doi:10.1016/j.joca.2012.11.003

Cited by 84 publications

(58 citation statements)

References 38 publications

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“…2012), we were tempted to further explore the role of HDL in the pathobiology of OA. For this purpose we applied histological, histomorphomentrical and molecular/biochemical methodologies and found that after the consumption of Western-type diet both LCAT and APOA1 deficient mice developed OA, in contrast to the control groups (Triantaphyllidou et al 2013). This, suggests that alterations in HDL biogenesis and maturation predispose to the development of OA in mice, following chronic insult with Western-type diet.…”

Section: The Effect Of the Components Of The Hdl Metabolic Pathways Omentioning

confidence: 99%

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High-density lipoprotein (HDL) metabolism and bone mass

Papachristou

Blair

Kypreos

et al. 2017

Journal of Endocrinology

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It is well appreciated that high density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in HDL metabolic pathways favor adipoblastic and restrain osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades. Increased bone marrow adiposity also deteriorates bone osteoblastic function and thus bone synthesis, leading to reduced bone mass. In this review, we present the current knowledge and the future directions with regards to the HDL-bone mass connection. Unraveling the molecular phenomena that underline this connection will promote the deeper understanding of the pathophysiology of bone-related pathologies, such as osteoporosis or bone metastasis, and pave the way towards the development of novel more effective therapies against these conditions.

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Section: The Effect Of the Components Of The Hdl Metabolic Pathways Omentioning

confidence: 99%

“…We have recently documented that in addition to its role in atheroprotection, APOA1 is also implicated in the development of non-alcoholic fatty liver disease as well as in the pathogenesis of osteoarthritis in mice (Karavia et al . 2012, Trantaphyllidou et al . 2013).…”

Section: The Effect Of the Components Of The Hdl Metabolic Pathways Omentioning

confidence: 99%

High-density lipoprotein (HDL) metabolism and bone mass

Papachristou

Blair

Kypreos

et al. 2017

Journal of Endocrinology

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“…22 Our research group has studied the role of HDL metabolic pathway in the pathogenesis of several diseases including osteoarthritis. [23][24][25] In fact, we have recently shown that apoA-1-and LCAT-deficient mice develop osteoarthritis when stressed with high-fat diet. 25 Triggered by the current knowledge and our research data in the present study we examined whether apoA-1 deficiency, and thus severely impaired HDL synthesis, affects the differentiation of bone marrow MSC in vitro and/or bone quality in vivo.…”

mentioning

confidence: 99%

“…[23][24][25] In fact, we have recently shown that apoA-1-and LCAT-deficient mice develop osteoarthritis when stressed with high-fat diet. 25 Triggered by the current knowledge and our research data in the present study we examined whether apoA-1 deficiency, and thus severely impaired HDL synthesis, affects the differentiation of bone marrow MSC in vitro and/or bone quality in vivo. Interestingly, we uncovered that the ApoA-1-deficient mice are severely osteoporotic with a complex phenotype that implicates HDL as a requirement for normal cell-fate selection in MSC in bone.…”

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confidence: 99%

Apolipoprotein A-1 regulates osteoblast and lipoblast precursor cells in mice

Blair

Kalyvioti

Papachristou

et al. 2016

Laboratory Investigation

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Imbalances in lipid metabolism affect bone homeostasis, altering bone mass and quality. A link between bone mass and high-density lipoprotein (HDL) has been proposed. Indeed, it has been recently shown that absence of the HDL receptor scavenger receptor class B type I (SR-B1) causes dense bone mediated by increased adrenocorticotropic hormone (ACTH). In the present study we aimed at further expanding the current knowledge as regards the fascinating bone-HDL connection studying bone turnover in apoA-1-deficient mice. Interestingly, we found that bone mass was greatly reduced in the apoA-1-deficient mice compared with their wild-type counterparts. More specifically, static and dynamic histomorphometry showed that the reduced bone mass in apoA-1 − / − mice reflect decreased bone formation. Biochemical composition and biomechanical properties of ApoA-1 − / − femora were significantly impaired. Mesenchymal stem cell (MSC) differentiation from the apoA-1 − / − mice showed reduced osteoblasts, and increased adipocytes, relative to wild type, in identical differentiation conditions. This suggests a shift in MSC subtypes toward adipocyte precursors, a result that is in line with our finding of increased bone marrow adiposity in apoA-1 − / − mouse femora. Notably, osteoclast differentiation in vitro and osteoclast surface in vivo were unaffected in the knock-out mice. In whole bone marrow, PPARγ was greatly increased, consistent with increased adipocytes and committed precursors. Further, in the apoA-1 − / − mice marrow, CXCL12 and ANXA2 levels were significantly decreased, whereas CXCR4 were increased, consistent with reduced signaling in a pathway that supports MSC homing and osteoblast generation. In keeping, in the apoA-1 − / − animals the osteoblast-related factors Runx2, osterix, and Col1a1 were also decreased. The apoA-1 − / − phenotype also included augmented CEPBa levels, suggesting complex changes in growth and differentiation that deserve further investigation. We conclude that the apoA-1 deficiency generates changes in the bone cell precursor population that increase adipoblast, and decrease osteoblast production resulting in reduced bone mass and impaired bone quality in mice.Laboratory Investigation (2016) 96, 763-772; doi:10.1038/labinvest.2016 published online 18 April 2016 Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone, resulting in bone fragility and fracture susceptibility. 1,2 It is a major public health problem worldwide; indeed, in the United States, more than 44 million people have osteoporosis or low bone mass. 3 The pathogenesis of osteoporosis is multifactorial. Age, sex, body size, metabolic factors, and genetic susceptibility are contributory factors. Interestingly, several studies have shown that there are strong links between bone, fat metabolism, and systemic energy metabolism, and that perturbations in lipid regulatory pathways may trigger both local and systemic phenomena that ultimately affect osteoblast and/or osteoclast function, resulting...

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“…Global Ldlr deletion, the gene encoding the LDL receptor, which plays a key role in the sequestration of circulating LDL cholesterol had no effect on cartilage health in collagenase-induced OA following a high cholesterol diet, but promoted ectopic bone formation and synovitis-like changes [38]. Alternatively, the presence of HDL appears critical to preventing cartilage destruction and OA, based on evidenced of increased cartilage degeneration and OA in apolipoprotein A-I-deficient mice consuming a Western diet [39]. This model is further supported by data from the investigation of hypercholesterolemia on the progression of OA, using a mouse model that closely mimics human lipoprotein metabolism and dyslipidemia.…”

Section: The Big Fat Metabolic Messmentioning

confidence: 99%

Novel Insights into Osteoarthritis Joint Pathology from Studies in Mice

Moon

Beier

2015

Curr Rheumatol Rep

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Osteoarthritis causes tremendous individual suffering and staggering societal costs, but due to our limited understanding of the underlying molecular and cellular mechanisms, our avenues for treating this disease are very restricted. Recent years have seen a drastic increase in the use of genetically modified mice to characterize the pathophysiology of osteoarthritis. Many new players and mechanisms driving osteoarthritis pathogenesis have been elucidated, some of which might be strong candidates as therapeutic targets for the human disease. The current review summarizes key findings (selected subjectively by the authors) from mouse osteoarthritis studies over recent years.

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Perturbations in the HDL metabolic pathway predispose to the development of osteoarthritis in mice following long-term exposure to western-type diet

Abstract: Our findings suggest that perturbations in HDL metabolism predispose to OA following chronic insult with WTD and raise the challenging possibility that HDL has a causative relation to OA in patients with metabolic syndrome.

Cited by 84 publications

References 38 publications

High-density lipoprotein (HDL) metabolism and bone mass

High-density lipoprotein (HDL) metabolism and bone mass

Apolipoprotein A-1 regulates osteoblast and lipoblast precursor cells in mice

Novel Insights into Osteoarthritis Joint Pathology from Studies in Mice

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