Correlation of Plasma Amino Acid Concentrations and Chondroprotective Effects of Glucosamine and Fish Collagen Peptide on the Development of Osteoarthritis

Ohnishi, Akihiro; Osaki, Tomohiro; Matahira, Yoshiharu; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Minami, Saburo

doi:10.1292/jvms.12-0241

Cited by 24 publications

(16 citation statements)

References 23 publications

(22 reference statements)

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“…This shows that acetate production from glucose is not necessary for the viability of T. brucei in vivo , suggesting that a possible acetate source (threonine) that is present in the blood is absent in the threonine-depleted in vitro culture medium. As mentioned above, mammalian blood contains approximately 150 µM threonine [35], [37], which is 10-times higher than in the threonine-depleted IMDM medium. The RNAi PDH.i cell line died in IMDM medium containing 15, 37.5 and 75 µM threonine, while addition of 150 µM of the amino acid restored its growth in vitro (Fig.…”

Section: Resultsmentioning

confidence: 91%

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Revisiting the Central Metabolism of the Bloodstream Forms of Trypanosoma brucei: Production of Acetate in the Mitochondrion Is Essential for Parasite Viability

et al. 2013

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BackgroundThe bloodstream forms of Trypanosoma brucei, the causative agent of sleeping sickness, rely solely on glycolysis for ATP production. It is generally accepted that pyruvate is the major end-product excreted from glucose metabolism by the proliferative long-slender bloodstream forms of the parasite, with virtually no production of succinate and acetate, the main end-products excreted from glycolysis by all the other trypanosomatid adaptative forms, including the procyclic insect form of T. brucei.Methodology/Principal FindingsA comparative NMR analysis showed that the bloodstream long-slender and procyclic trypanosomes excreted equivalent amounts of acetate and succinate from glucose metabolism. Key enzymes of acetate production from glucose-derived pyruvate and threonine are expressed in the mitochondrion of the long-slender forms, which produces 1.4-times more acetate from glucose than from threonine in the presence of an equal amount of both carbon sources. By using a combination of reverse genetics and NMR analyses, we showed that mitochondrial production of acetate is essential for the long-slender forms, since blocking of acetate biosynthesis from both carbon sources induces cell death. This was confirmed in the absence of threonine by the lethal phenotype of RNAi-mediated depletion of the pyruvate dehydrogenase, which is involved in glucose-derived acetate production. In addition, we showed that de novo fatty acid biosynthesis from acetate is essential for this parasite, as demonstrated by a lethal phenotype and metabolic analyses of RNAi-mediated depletion of acetyl-CoA synthetase, catalyzing the first cytosolic step of this pathway.Conclusions/SignificanceAcetate produced in the mitochondrion from glucose and threonine is synthetically essential for the long-slender mammalian forms of T. brucei to feed the essential fatty acid biosynthesis through the “acetate shuttle” that was recently described in the procyclic insect form of the parasite. Consequently, key enzymatic steps of this pathway, particularly acetyl-CoA synthetase, constitute new attractive drug targets against trypanosomiasis.

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Section: Resultsmentioning

confidence: 91%

“…Incubation of the parasites in threonine-depleted medium, which contains only ∼15 µM of the amino acid coming from FCS [35], did not affect growth of the wild-type and RNAi PDH.ni cells, while growth of the RNAi PDH.i mutant was abolished (Fig. 6D).…”

Section: Resultsmentioning

confidence: 95%

Revisiting the Central Metabolism of the Bloodstream Forms of Trypanosoma brucei: Production of Acetate in the Mitochondrion Is Essential for Parasite Viability

et al. 2013

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“…Arginine supplementation may prevent and treat osteoporosis, especially in older women 25 . Although there is still a lack of human data, high plasma arginine concentration has been correlated with low histological severity score of cartilage in the rabbit OA model induced by anterior cruciate ligament transection 26 . Thus the depletion of arginine in OA observed in the current study may be interpreted as the attempt to repair the damaged cartilage by producing more ornithine, proline, and polyamines.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients

Zhang

Sun

Likhodii

et al. 2016

Osteoarthritis and Cartilage

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“…Recently, dog owners and veterinarians have considered managing osteoarthritis in dogs with herbs and nutraceuticals. Today, in humans and animals, glucosamine and chondroitin sulfate are the most common nutraceuticals to provide building blocks to repair the cartilage and to minimize and slow down the progression of osteoarthritis to ease inflammatory pain [24,25,[34][35][36][37].…”

Section: Anti-inflammatory and Anti-arthritic Efficacy And Safety Of mentioning

confidence: 99%

Anti-Inflammatory and Anti-Arthritic Efficacy and Safety of Purified Shilajit in Moderately Arthritic Dogs

Lawley¹,

Rc²,

Jt³

et al. 2013

Journal of Veterinary Science and Animal Husbandry

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The objective of this investigation was to evaluate the efficacy and safety of purified Shilajit in moderately arthritic dogs. Ten clientowned dogs in a randomized double-blinded study received either a placebo or Shilajit (500 mg) twice daily for a period of five months. Dogs were evaluated each month for physical condition (body weight, body temperature, heart rate, and respiration rate) and pain associated with arthritis (overall pain, pain from limb manipulation, and pain after physical exertion). Serum samples collected from these dogs were examined each month for biomarkers of liver (bilirubin, ALT, and AST), kidney (BUN and creatinine) heart and muscle (creatine kinase) functions. The findings of this study revealed that dogs receiving Shilajit (Group-II) showed a significant (P<0.05) reduction in pain from limb manipulation by day 60, and overall pain and pain after physical exertion by day 120. Maximum pain reduction, using all three criteria, was observed on day 150. Pain level remained significantly unchanged in dogs receiving the placebo. Dogs in either group showed no significant change (P>0.05) in physical parameters or serum markers, suggesting that Shilajit was well tolerated by moderately arthritic dogs. It was concluded that Shilajit significantly (P<0.05) reduced pain in osteoarthritic dogs and markedly improved their daily life without any side effects. Currently, there are more than 78 million dogs in the US, and every fifth adult dog suffers from arthritis [1]. Dogs suffer more frequently from osteoarthritis (a chronic and progressive disease) than any other form of arthritis. Osteoarthritis, also known as degenerative joint disease, is a functional disorder of the joint, characterized by a change in joint shape secondary to a loss of articular cartilage, osteophyte formation, subchondral sclerosis, bone marrow lesions and synovial proliferation, with subsequent alteration of mechanical properties that result in decreased stability, movement and loading [2-9]. In the early stages of osteoarthritis, there is a progressive depletion of the cartilage proteoglycan leading to a net loss of matrix from the cartilage [10]. This leads to a cascade of negative events, including changes in enzymatic cleavage of proteoglycans and an increase in minor collagen types leading to structural damage and deterioration of the cartilage. The breakdown of cartilage can be increased with certain enzymes including the matrix metalloproteinase enzymes (MMPs). The severity of cartilage lesions in osteoarthritis can be cor

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Correlation of Plasma Amino Acid Concentrations and Chondroprotective Effects of Glucosamine and Fish Collagen Peptide on the Development of Osteoarthritis

Cited by 24 publications

References 23 publications

Revisiting the Central Metabolism of the Bloodstream Forms of Trypanosoma brucei: Production of Acetate in the Mitochondrion Is Essential for Parasite Viability

Revisiting the Central Metabolism of the Bloodstream Forms of Trypanosoma brucei: Production of Acetate in the Mitochondrion Is Essential for Parasite Viability

Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients

Anti-Inflammatory and Anti-Arthritic Efficacy and Safety of Purified Shilajit in Moderately Arthritic Dogs

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