Can urinary CTX-II be a biomarker for knee osteoarthritis?

Arunrukthavon, P.; Heebthamai, Danai; Benchasiriluck, Prapasri; Chaluay, Supinda; Chotanaphuti, Thanainit; Khuangsirikul, Saradej

doi:10.1186/s42836-020-0024-2

Cited by 19 publications

(19 citation statements)

References 34 publications

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“…In our study, the urinary CTX-II levels showed an inverse correlation with some of the KOOS domains scores, showing that a higher level of knee-related problems was reflected in a higher level of urinary CTX-II. This is in accordance with previous studies using the patient-reported outcome of WOMAC index ( 38 ). This observed correlation may explain the beneficial effect of GSM on both urinary CTX-II and the KOOS domains, while COMP levels were not affected.…”

Section: Discussionsupporting

confidence: 93%

“…The lack of effect of GSM on urinary CTX-II could be due to high levels of urinary CTX-II at baseline (571.6 ± 415.6 ng/mmol Cr), which were higher than the values from a previous study (511.92 ± 486.21 ng/mmol Cr) using the same ELISA kit in elderly females with knee OA (age 64.45 ± 10.6 years) (38). Thus, due to high levels of urinary CTX-II, a notable reduction may not have been detected after 12 weeks of GSM treatment, and longer duration may result in a more significant effect.…”

Section: Discussioncontrasting

confidence: 68%

“…Stratifying based on age and adjusting the baseline VAS pain score helped to negate this effect to some extent. Secondly, higher levels of urinary CTX-II in women than men were reported in a previous study (38), which was partly explained by the effects of menopause, and thus a male population may respond better to GSM supplementation. The effects of diurnal variation on biomarker levels should be taken into consideration.…”

Section: Discussionmentioning

confidence: 77%

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Effects of Greenshell™ mussel intervention on biomarkers of cartilage metabolism, inflammatory markers and joint symptoms in overweight/obese postmenopausal women: A randomized, double-blind, and placebo-controlled trial

et al. 2022

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ObjectiveTo investigate the effect of whole greenshell mussel (GSM) powder on biomarkers of cartilage metabolism, inflammatory cytokines, and joint symptoms in postmenopausal women with overweight/obesity and joint discomfort.DesignFifty-five postmenopausal women with overweight/obesity were randomly assigned to receive 3 g/day whole GSM powder or placebo for 12 weeks. Cartilage turnover biomarkers urinary C-telopeptide of type II collagen (CTX-II) and serum cartilage oligomeric matrix protein (COMP) were measured at baseline, week 6 and 12. Plasma cytokines were measured at baseline and week 12. Joint pain and knee-related problems were assessed at baseline and week 12 using a 100 mm Visual Analogue Scale (VAS) and the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, respectively.ResultsForty-nine participants completed the study (GSM n = 25, placebo n = 24). After 12 weeks, urinary CTX-II showed no significant change over time or between the groups (interaction effect P = 0.1). However, in women with symptomatic knees, a significant difference was noted between the group (treatment effect P = 0.04), as it was lower in the GSM group compared to placebo group at week 6 (P = 0.04) and week 12 (P = 0.03). Serum COMP and plasma cytokines were not affected. GSM supplementation showed greater reduction in the VAS pain score than placebo (−13.2 ± 20.3 vs. −2.9 ± 15.9; P = 0.04). No significant change in KOOS domains between the two groups was observed.ConclusionOral supplementation of whole GSM powder at 3 g/day may slow down the degradation of type II collagen in postmenopausal women with symptomatic knees. GSM treatment conferred clinical benefit on overall joint pain. No significant effect was noted for inflammatory cytokines, suggesting that GSM may act within the joint microenvironment rather than at the systemic level.Clinical trial registration[www.australianclinicaltrials.gov.au/clinical-trialregistries], identifier [ACTRN12620000413921p].

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 68%

Section: Discussionmentioning

confidence: 77%

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Effects of Greenshell™ mussel intervention on biomarkers of cartilage metabolism, inflammatory markers and joint symptoms in overweight/obese postmenopausal women: A randomized, double-blind, and placebo-controlled trial

et al. 2022

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“…In this study, we were only able to measure the concentration of sCOMP, sPIICP, and sHA despite other biomarkers such as PIIANP [ 39 ], C-telopeptide of type II collagen (CTX-II) [ 67 , 71 ], and synovial cytokines [ 72 ], and others [ 19 ] have been reported. Moreover, there was a statistical limitation because the relationship between each of the three biomarkers and the severity of OA and other OA risk factors was assessed using two tests, linear regression analysis, and Spearman’s Correlation test.…”

Section: Discussionmentioning

confidence: 99%

Associations between serum biomarkers of cartilage metabolism and serum hyaluronic acid, with risk factors, pain categories, and disease severity in knee osteoarthritis: a pilot study

Papaneophytou

Alabajos-Cea

Viosca-Herrero

et al. 2022

BMC Musculoskelet Disord

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Background Specific serum biomarkers of cartilage metabolism such as cartilage oligomeric matrix protein (sCOMP) and procollagen type II C-terminal propeptide (sPIICP) as well as hyaluronan (sHA), a biomarker of synovitis, have been implicated in the pathophysiology of knee osteoarthritis (OA). However, the associations of these biomarkers with the severity of the disease and OA risk factors, including age and obesity remain inconclusive. This analysis examines the associations between these serum biomarkers and the radiographic severity of OA and knee pain, as wells as obesity, the age and gender of the participants, and other OA risk factors. Methods From 44 patients with early knee OA and 130 patients with late knee OA we analyzed the radiographic severity of the disease using the Kellgren and Lawrence (KL) grading system. Moreover, 38 overweight healthy individuals were used as a control group. Specific information was collected from all participants during their recruitment. The levels of the three serum biomarkers were quantified using commercially available ELISA kits. Serum biomarkers were analyzed for associations with the average KL scores and pain in both knees, as well as with specific OA risk factors. Results The levels of sCOMP were elevated in patients with severe late OA and knee pain and correlated weakly with OA severity. A weakly correlation of sHA levels and OA severity OA was observed. We demonstrated that only sPIICP levels were markedly decreased in patients with late knee OA suggesting the alterations of cartilage metabolism in this arthritic disease. Moreover, we found that sPIICP has the strongest correlation with obesity and the severity of OA, as well as with the knee pain at rest and during walking regardless of the severity of the disease. ROC analysis showed that the area under the ROC curve (AUC) was 0.980 (95% CI: 0.945–0.995; p < 0.0001), suggesting high diagnostic accuracy of sPIICP. Interestingly, gender and age had also an effect on the levels of sPIICP. Conclusion This study revealed the potential of serum PIICP to be used as a biomarker to monitor the progression of knee OA, however, further studies are warranted to elucidate its clinical implication.

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“…Additionally, sympathectomy reduced the degradation of type II collagen as indicated by reduced serum CTX-II levels compared to WT DMM mice. CTX-II was also demonstrated to be higher in spontaneous osteoarthritic mice (Watari et al 2011) and in knee-OA patients compared to healthy ones (Arunrukthavon et al 2020). The increased CTX-II level in WT mice after 4 weeks suggests that type II collagen degradation begins at the early stage of OA development.…”

Section: The Protective Effect Of Sympathectomy In Oa Cartilagementioning

confidence: 95%

Sympathetic influences on articular cartilage regeneration capacity and osteoarthritis manifestation

Bagdadi¹

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The pathogenesis of osteoarthritis (OA) involves articular cartilage, synovial tissue and subchondral bone and is therefore a disease of the whole joint. OA is characterized by progressive degradation of cartilage, synovial inflammation, osteophyte formation and subchondral bone sclerosis. Cartilage-surrounding tissues are innervated by tyrosine hydroxylase (TH)-positive sympathetic nerve fibers with the most important sympathetic neurotransmitter norepinephrine (NE) detected in the synovial fluid of OA patients. Furthermore, adrenergic receptors are expressed in different knee joint tissues. Most in vitro studies indicate a potential role of the β2-adrenergic receptor, which has been not investigated during OA pathogenesis in vivo. The role of the sympathetic nervous system (SNS) in OA progression has not yet been studied. Therefore, the objective of this study was to analyze how the SNS and NE influence the MSC dependent cartilage regeneration in vitro and the OA pathogenesis and manifestation in vivo. In the first part of this study, the effect of NE on the chondrogenesis of sASC, which are known to play an important role in cartilage regeneration was analyzed in vitro. In the second part of this study, the role of the SNS was studied in vivo in mice that were sympathectomized chemically followed by surgically induced OA. The specific focus was on the β2-adrenergic receptor effects on OA pathogenesis, which were analyzed in β2-adrenergic receptor-deficient mice. The in vitro experiments have shown that NE reduced the chondrogenic potential of sASCs by decreasing the expression of type II collagen and sGAG. NE mediated these effects mainly by the α2-AR signalling. Furthermore, NE treatment led to activation of the ERK1/2 signal pathway. These findings suggested that the sympathetic neurotransmitter NE might suppress the chondrogenic capacity of MSC and their dependent cartilage regeneration and may also play a role in OA progression and manifestation. The in vivo study has shown that sympathectomy reduced synovial TH-positive nerve fibers in the synovium and the NE concentration in the spleen significantly. In WT mice, DMM leads to increased NE concentrations in the spleen compared to sham mice indicating an increased SNS activity after mechanical stress or inflammation due to DMM. Sympathectomy leads to less pronounced cartilage degeneration (OARSI score) after DMM compared to DMM in WT mice. Furthermore, the release of the type II collagen degradation fragment CTX-II was abolished in Syx DMM mice compared to WT DMM mice, suggesting that less SNS activity due to sympathectomy reduced the cartilage degeneration during OA pathogenesis. Similarly, sympathectomy decreased the synovitis score significantly after DMM compared to DMM in WT mice. Synovitis in WT mice was accompanied by increased MMP-13 expression in the synovium after DMM, compared to Syx mice. Cartilage degeneration seemed to be driven mainly by the increased synovial inflammation accompanied by an increased MMP13 expression in synoviocytes and not in chondrocytes. The pathological changes in synovium and cartilage might also be linked to each other, as indicated by the moderate correlation between the synovial inflammation (synovitis score) and cartilage degeneration (OARSI score). Subchondral bone volume as well the thickness of the subchondral bone plate (SCBP) and calcified cartilage (CC) were increased in Syx mice compared to WT after DMM. The data on DMM induction in β2-AR deficient mice revealed that the β2-AR signaling is involved in cartilage degeneration and the aggravated subchondral bone changes as these mice had less pronounced cartilage degeneration compared to WT mice. While the cartilage degeneration was similar, the subchondral bone changes were more pronounced in β2-AR deficient mice compared to the Syx mice. Overall, the SNS had differential effects in cartilage, synovium and subchondral bone. A reduced SNS activity by sympathectomy attenuated cartilage degeneration and synovitis but aggravated the OA specific subchondral bone changes. These findings provide new insights into the development of novel therapeutic strategies for OA by targeting the SNS in a tissue- specific manner.

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Can urinary CTX-II be a biomarker for knee osteoarthritis?

Cited by 19 publications

References 34 publications

Effects of Greenshell™ mussel intervention on biomarkers of cartilage metabolism, inflammatory markers and joint symptoms in overweight/obese postmenopausal women: A randomized, double-blind, and placebo-controlled trial

Effects of Greenshell™ mussel intervention on biomarkers of cartilage metabolism, inflammatory markers and joint symptoms in overweight/obese postmenopausal women: A randomized, double-blind, and placebo-controlled trial

Associations between serum biomarkers of cartilage metabolism and serum hyaluronic acid, with risk factors, pain categories, and disease severity in knee osteoarthritis: a pilot study

Sympathetic influences on articular cartilage regeneration capacity and osteoarthritis manifestation

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