Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells

Haywood, Jamie; Yammani, Raghunatha R.

doi:10.1016/j.joca.2015.11.020

Cited by 49 publications

(59 citation statements)

References 16 publications

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“…The unexpected similarities between ACLR- and sham-operated knee joints may have different explanations. The BW may be a risk factor to develop OA as discussed by [80,81] also for metabolic factors. The GM used in the presented study had a mean BW of 55kg at an age of approx.…”

Section: Discussionmentioning

confidence: 99%

Osteoarthritis in the Knee Joints of Göttingen Minipigs after Resection of the Anterior Cruciate Ligament? Missing Correlation of MRI, Gene and Protein Expression with Histological Scoring

et al. 2016

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IntroductionThe Göttingen Minipig (GM) is used as large animal model in articular cartilage research. The aim of the study was to introduce osteoarthritis (OA) in the GM by resecting the anterior cruciate ligament (ACLR) according to Pond and Nuki, verified by histological and magnetic resonance imaging (MRI) scoring as well as analysis of gene and protein expression.Materials and MethodsThe eight included skeletally mature female GM were assessed after ACLR in the left and a sham operation in the right knee, which served as control. 26 weeks after surgery the knee joints were scanned using a 3-Tesla high-field MR tomography unit with a 3 T CP Large Flex Coil. Standard proton-density weighted fat saturated sequences in coronal and sagittal direction with a slice thickness of 3 mm were used. The MRI scans were assessed by two radiologists according to a modified WORMS-score, the X-rays of the knee joints by two evaluators. Osteochondral plugs with a diameter of 4mm were taken for histological examination from either the main loading zone or the macroscopic most degenerated parts of the tibia plateau or condyle respectively. The histological sections were blinded and scored by three experts according to Little et al. Gene expression analysis was performed from surrounding cartilage. Expression of adamts4, adamts5, acan, col1A1, col2, il-1ß, mmp1, mmp3, mmp13, vegf was determined by qRT-PCR. Immunohistochemical staining (IH) of Col I and II was performed. IH was scored using a 4 point grading (0—no staining; 3-intense staining).Results and DiscussionSimilar signs of OA were evident both in ACLR and sham operated knee joints with the histological scoring result of the ACLR joints with 6.48 ± 5.67 points and the sham joints with 6.86 ± 5.84 points (p = 0.7953) The MRI scoring yielded 0.34 ± 0.89 points for the ACLR and 0.03 ± 0.17 for the sham knee joints. There was no correlation between the histological and MRI scores (r = 0.10021). The gene expression profiles as well as the immunohistochemical findings showed no significant differences between ACLR and sham knee joints. In conclusion, both knee joints showed histological signs of OA after 26 weeks irrespective of whether the ACL was resected or not. As MRI results did not match the histological findings, MRI was obviously unsuitable to diagnose the OA in GM. The analysis of the expression patterns of the 10 genes could not shed light on the question, whether sham operation also induced cartilage erosion or if the degeneration was spontaneous. The modified Pond-Nuki model may be used with reservation in the adult minipig to induce an isolated osteoarthritis.

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Section: Discussionmentioning

confidence: 99%

Osteoarthritis in the Knee Joints of Göttingen Minipigs after Resection of the Anterior Cruciate Ligament? Missing Correlation of MRI, Gene and Protein Expression with Histological Scoring

et al. 2016

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“…FFAs (palmitate and oleate) were conjugated to low-endotoxin, fatty acid-free bovine serum albumin as described previously [16]. For experiments, BSA-FFA conjugate was diluted in culture media and low endotoxin, fatty acid free albumin was used as an experimental control.…”

Section: Methodsmentioning

confidence: 99%

High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes

Nazli

Loeser

Chubinskaya

et al. 2017

Osteoarthritis and Cartilage

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Introduction Insulin-like growth factor-1 (IGF-1) promotes matrix synthesis and cell survival in cartilage. Chondrocytes from aged and osteoarthritic cartilage have a reduced response to IGF-1. The purpose of this study was to determine the effect of free fatty acids present in a high-fat diet on IGF-1 function in cartilage and the role of ER stress. Methods C57BL/6 male mice were maintained on either a high-fat (60% kcal from fat) or a low-fat (10% kcal from fat) diet for 4 months. Mice were then sacrificed; femoral head cartilage caps were collected and treated with IGF-1 to measure proteoglycan synthesis. Cultured human chondrocytes were treated with 500μM free fatty acids palmitate or oleate, followed by stimulation with (100 ng/ml) IGF-1 overnight to measure CHOP (a protein marker for ER stress) and proteoglycan synthesis. Human chondrocytes were pre-treated with palmitate or 1mM 4-phenyl butyric acid (PBA) or 1μM JNK inhibitor, and IGF-1 function (PG synthesis and signaling) was measured. Results Cartilage explants from mice on the high fat-diet showed reduced IGF-1 mediated proteoglycan synthesis compared to a low-fat group. Treatment of human chondrocytes with palmitate induced expression of CHOP, activated JNK and inhibited IGF-1function. PBA, a small molecule chemical chaperone that alleviates ER stress rescued IGF-1 function and a JNK inhibitor rescued IGF-1 signaling. Conclusions Palmitate-induced ER stress inhibited IGF-1 function in chondrocytes/cartilage via activating the MAP kinase JNK. This is the first study to demonstrate that ER stress is metabolic factor that regulates IGF-1 function in chondrocytes.

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“…Palmitic acid, a saturated fatty acid that is a physiological component in human follicular fluid, is a potential physiological inducer of ER stress (Danino et al, 2015; Haywood and Yammani, 2015). Exposure of COCs to a high dose of palmitic acid can induce ER stress and the UPR, accompanied with reduced secretion of PTX3 (a protein marker for oocyte development and fertilization; (Zhang et al, 2005; Baranova et al, 2014), mitochondrial dysfunction and impaired oocyte maturation, and fertilization.…”

Section: Obesity and Aberrant Activation Of The Upr In The Ovarymentioning

confidence: 99%

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

Qiao

2016

Protein &Amp; Cell

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The endoplasmic reticulum (ER) is the principal organelle responsible for several specific cellular functions including synthesis and folding of secretory or membrane proteins, lipid metabolism, and Ca2+ storage. Different physiological as well as pathological stress conditions can, however, perturb ER homeostasis, giving rise to an accumulation of unfolded or misfolded proteins in the ER lumen, a condition termed ER stress. To deal with an increased folding demand, cells activate the unfolded protein response (UPR), which is initially protective but can become detrimental if ER stress is severe and prolonged. Accumulating evidence demonstrates a link between the UPR and ovarian development and function, including follicular growth and maturation, follicular atresia, and corpus luteum biogenesis. Additionally, ER stress and the UPR may also play an important role in the ovary under pathological conditions. Understanding the molecular mechanisms related to the dual role of unfolded protein response in the ovarian physiology and pathology may reveal the pathogenesis of some reproductive endocrine diseases and provide a new guidance to improve the assisted reproductive technology. Here we review the current literature and discuss concepts and progress in understanding the UPR, and we also analyze the role of ER stress and the UPR in the ovary.

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Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells

Cited by 49 publications

References 16 publications

Osteoarthritis in the Knee Joints of Göttingen Minipigs after Resection of the Anterior Cruciate Ligament? Missing Correlation of MRI, Gene and Protein Expression with Histological Scoring

Osteoarthritis in the Knee Joints of Göttingen Minipigs after Resection of the Anterior Cruciate Ligament? Missing Correlation of MRI, Gene and Protein Expression with Histological Scoring

High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

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