Ascorbate modulation of chondrocyte gene expression is independent of its role in collagen secretion.

Sullivan, T.A.; Uschmann, Barbara D.; Hough, R. B.; Leboy, Phoebe S.

doi:10.1016/s0021-9258(17)31675-7

Cited by 59 publications

(6 citation statements)

References 40 publications

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“…The largest number of matched hits was for ascorbate and aldarate metabolism, phenylalanine, linoleic, and arginine, and proline metabolism. Notable contributions came from metabolites attributed to ascorbate and proline metabolism, suggesting variation in collagen production and thus differences in cell matrix features. − Although ascorbate is instrumental in collagen production, it is expected that the variance observed with ascorbate metabolism has been somewhat biased by the inclusion of ascorbate-2-phosphate as a component of the OIM culture media. Linoleic acid metabolism, which contributes to the differences noted between sample types, is known to play an important role in bone development − as well as acting as precursor for a class of broad range cell membrane signaling molecules (eicosanoids), inferring significant differences in cellular regulation …”

Section: Resultsmentioning

confidence: 99%

Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis

et al. 2017

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It is counterintuitive that invertebrate shells can induce bone formation, yet nacre, or mother of pearl, from marine shells is both osteoinductive and osteointegrative. Nacre is composed of aragonite (calcium carbonate) and induces production of vertebrate bone (calcium phosphate). Exploited by the Mayans for dental implants, this remarkable phenomenon has been confirmed in vitro and in vivo, yet the characteristic of nacre that induces bone formation remains unknown. By isolating nacre topography from its inherent chemistry in the production of polycaprolactone (PCL) nacre replica, we show that, for mesenchymal stem cells, nacre topography is osteoinductive. Gene expression of specific bone marker proteins, osteopontin, osteocalcin, osteonectin, and osterix, is increased 10-, 2-, 1.7-, and 1.8-fold, respectively, when compared to planar PCL. Furthermore, we demonstrate that bone tissue that forms in response to the physical topographical features of nacre has a higher crystallinity than bone formed in response to chemical cues with a full width half-maximum for PO Raman shift of 7.6 ± 0.7 for mineral produced in response to nacre replica compared to a much broader 34.6 ± 10.1 in response to standard osteoinductive medium. These differences in mineral product are underpinned by differences in cellular metabolism. This observation can be exploited in the design of bone therapies; a matter that is most pressing in light of a rapidly aging human population.

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Section: Resultsmentioning

confidence: 99%

Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis

et al. 2017

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“…Furthermore, it appeared that collagen matrix derived in vitamin C treated chondrocytes was more stable as indicated by diminished spontaneous release of labeled collagen. Most likely this may be attributed to collagen hydroxylation and stable secreted triple-helical collagen 24,25 . In contrast, vitamin C treatment of chondrocytes did not influence reactivity to lipid oxidative stress induced by calcium ionophore.…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin C is well documented to cause collagen hydroxylation by modification of prolyl and lysl residues 24,25 . Connective tissue cells including chondrocytes cultured in absence of vitamin C result in collagen underhydroxylation with impaired collagen secretion 24 .…”

Section: Introductionmentioning

confidence: 99%

Malondialdehyde oxidation of cartilage collagen by chondrocytes

Tiku¹,

Allison²,

Naik³

et al. 2003

Osteoarthritis and Cartilage

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These observations suggest that collagen hydroxylation of matrix by vitamin C does not play a role in this model of chondrocyte-dependent collagen degradation. Also, this study demonstrates that chondrocyte-derived lipid peroxidation product MDA mediates oxidation of cartilage collagens. Oxidative modification of cartilage collagen in vivo could result in alteration of biochemical and biophysical properties of cartilage collagen fibrils, making them prone to degradation, thus initiating the changes observed in aging and OA.

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“…10,11 It also has other important functions in the formation of non-collagenous proteins during bone healing, development of mesenchymal, chondroblast, and osteogenic phenotypes. [12][13][14][15] Also, it has been found that vitamin C deficiency leads to delaying in healing of bone fractures. [16][17][18] Although some authors have reported beneficial effects of vitamin C, others warn that in the presence of metals such as iron with vitamin C could generate more free radicals via the Fenton reaction.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and bone markers in plasma of patients with long-bone fixative surgery: Role of antioxidants

et al. 2010

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It is well known that bone markers (e.g. osteocalcin and alkaline phosphatase) play a significant role in healing of bone fractures, whereas oxidative stress delay such healing. The present study aimed to investigate the effect of a mixture of antioxidants (vitamins A, C, E, and selenium) on oxidative stress parameters, and the levels of bone healing markers in the plasma of male patients following fixative surgery of long bones. Antioxidant tablets (300 µg vitamin A, 10 mg vitamin E, 60 mg vitamin C, and 75 µg selenium) were administered to groups 3 and 4 (10 patients in each) for 1 and 2 weeks, respectively, in addition to the regular postoperative treatment. Groups 1 (25 patients) and 2 (10 patients) received the regular post-operative treatment consisting of intravenous (I.V.) second generation of cephalosporin 1000 mg/day for 3 days, oral diclofenac 50 mg, and paracetamol 500 mg twice daily for 15 days. Osteocalcin level and alkaline phosphatase activity as well as antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR), as well as glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) as indices of oxidative stress, were determined in the plasma of all patients after 1 or 2 weeks of long-bone fixative surgery. The results revealed that osteocalcin level and the activity of alkaline phosphatase were markedly increased in the plasma of patients who received antioxidants for 2 weeks. In addition, after 1 and/or 2 weeks, the levels of TBARS were significantly lower in the antioxidant-treated patients compared with those who did not receive antioxidants. On the other hand, the activities of SOD and GR were markedly elevated in plasma of patients who received antioxidants after 1 or 2 weeks compared with patients who received regular therapy. Moreover, the level of plasma GSH was markedly increased only after 2 weeks in patients who received antioxidants. It is concluded that administration of antioxidant vitamins A, E, and C in addition to selenium could accelerate bone healing after long-bone fixative surgery. Therefore, antioxidants should be considered in designing therapeutic protocols in post-operative bone surgery.

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Ascorbate modulation of chondrocyte gene expression is independent of its role in collagen secretion.

Cited by 59 publications

References 40 publications

Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis

Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis

Malondialdehyde oxidation of cartilage collagen by chondrocytes

Oxidative stress and bone markers in plasma of patients with long-bone fixative surgery: Role of antioxidants

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