The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal... Show moreThe PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO trial, a 24-month prospective, multicenter, open-label, randomized, controlled trial aimed at comparing everolimus-based vs. cyclosporine-based immunosuppression. PRO-C6 was measured in plasma and urine samples collected 6 and 24 months post-transplantation. Fibrosis was evaluated in biopsies collected at the same time points by Banff interstitial fibrosis/tubular atrophy (IF/TA) scoring and collagen staining (Picro Sirius Red; PSR); inflammation was evaluated by the tubulo-interstitial inflammation score (ti-score). Linear regression analyses were performed. Six-month plasma PRO-C6 was cross-sectionally associated with IF/TA score (Std. beta = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. beta = 0.24 and 0.23, respectively) (p < 0.05 for all). No significant associations were found between urine PRO-C6 and any of the biopsy findings. Fibrotic changes and urine PRO-C6 behaved differentially over time according to immunosuppressive therapy. These results are a first step towards non-invasive fibrosis detection after kidney transplantation by means of collagen VI synthesis measurement, and further research is required. Show less
OBJECTIVE: Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between... Show moreOBJECTIVE: Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between tissues actively contributes to homeostasis. In the current review, we try to define a subtype of osteoarthritis (OA), metabolic OA, which is dependent on an unhealthy phenotype. METHODS: Peer-reviewed research articles and reviews were reviewed and summarized. Only literature readily available online, either by download or by purchase order, was included. RESULTS: OA is the most common joint disease and is more common in women after menopause. OA is a disease that affects the whole joint, including cartilage, subchondral bone, synovium, tendons, and muscles. The clinical endpoints of OA are pain and joint space narrowing, which is characterized by cartilage erosion and subchondral sclerosis, suggesting that cartilage is a central tissue of joint health. Thus, the joint, more specifically the cartilage, may be considered a target of endocrine function in addition to the well-described traditional risk factors of disease initiation and progression such as long-term loading of the joint due to obesity. Metabolic syndrome affects a range of tissues and may in part be molecularly described as a dysregulation of cytokines, adipokines, and hormones (eg, estrogen and thyroid hormone). Consequently, metabolic imbalance may both directly and indirectly influence joint health and cartilage turnover, altering the progression of diseases such as OA. CONCLUSIONS: There is substantial evidence for a connection between metabolic health and development of OA. We propose that more focus be directed to understanding this connection to improve the management of menopausal health and associated comorbidities. Show less
Bos, S.D.; Beekman, M.; Maier, A.B.; Karsdal, M.A.; Kwok, W.Y.; Bay-Jensen, A.C.; ... ; Meulenbelt, I. 2012
OBJECTIVES: Individual metabolic characteristics and age-related changes may affect osteoarthritis (OA) risk as well as levels of potential OA biomarkers such as serum cartilage oligomeric protein ... Show moreOBJECTIVES: Individual metabolic characteristics and age-related changes may affect osteoarthritis (OA) risk as well as levels of potential OA biomarkers such as serum cartilage oligomeric protein (sCOMP) and urinary cross-linked C-telopeptide of type 2 collagen (uCTX2). We investigated hand OA and these putative OA biomarker characteristics at different ages in individuals with a propensity for healthy ageing, in controls, and in patients with OA. METHODS: We investigated hand radiological OA (ROA) and levels of sCOMP and uCTX2 in the Leiden Longevity Study, which consisted of the middle-aged offspring of long-lived sibling pairs as metabolically healthy agers and their partners as controls, and for ROA we compared patients with OA at multiple joint sites from the Genetics, osteoARthritis and Progression Study with the healthy agers and controls. RESULTS: Hand ROA mean scores were lower in the healthy agers than in controls. Lower hand ROA scores at higher ages were observed in healthy agers with low glucose levels. Furthermore, in healthy agers, a higher mean sCOMP level was observed than in controls. All study groups had higher sCOMP levels at higher chronological age. Likewise, uCTX2 levels were higher at higher chronological age in the controls and patients with OA, which was not observed in the healthy agers. CONCLUSIONS: Metabolic health in middle age is associated with less ROA and influences putative OA marker profiles, independently of chronological age. When used as OA biomarkers, it is relevant that independently of hand ROA status, uCTX2 is influenced by healthy metabolism and sCOMP is higher at higher chronological age. Show less
