Serum Propeptide Of Type Research Articles

Associations between biomarkers of matrix metabolism and inflammation with pain and fatigue in participants suspected of early hip and or knee osteoarthritis: data from the CHECK study

To assess the associations of biomarkers in serum [highsensitivity C-reactive protein (hs-CRP), serum cartilage oligomeric protein (sCOMP), serum propeptide of type I procollagen (sPINP) and serum osteocalcin (sOC)] and urine [urinary type II collagen telopeptide (uCTX-2)] with the extent and progression of nocturnal pain, pain while walking, and fatigue in participants with hip and/or knee pain suspected to be early stage osteoarthritis (OA). hs-CRP, uCTX-2, sCOMP, sPINP and sOC were measured at baseline in 1,002 participants of the Cohort Hip and Cohort Knee (CHECK). Nocturnal pain, pain while walking and fatigue were assessed by self-reported questionnaires at baseline and 2-year follow-up. Associations between these biomarkers and symptoms were examined using logistic and linear regression analyses. hs-CRP was significantly associated with mild nocturnal pain (OR 1.18 95% CI 1.01-1.37), with mild and moderate pain while walking (OR 1.17 95% CI 1.01-1.35 and OR 1.56 95% CI 1.29-1.90, respectively) and with progression of nocturnal pain (OR 1.25 95% CI 1.07-1.46). uCTX-2 was associated with mild nocturnal pain (OR 1.40 95% CI 1.05-1.85) and with mild and severe-extreme pain while walking (OR 1.35 95% CI 1.04-1.75 and OR 2.55 95% CI 1.03-6.34, respectively). sPINP was associated with severe-extreme nocturnal pain (OR 0.45 95% CI 0.25-0.82). No significant associations were found for sCOMP and sOC, nor for any of the biomarkers and fatigue. This study of biomarkers in a large cohort of participants with hip and/or knee pain suspected to reflect early stage hip and/or knee OA suggests that inflammation and cartilage matrix degeneration play a role in pain, but not in fatigue.

The Sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice.

Estrogen deficiency leads to rapid bone loss and skeletal fragility. Sclerostin, encoded by the sost gene, and a product of the osteocyte, is a negative regulator of bone formation. Blocking sclerostin increases bone mass and strength in animals and humans. Sirtuin1 (Sirt1), a player in aging and metabolism, regulates bone mass and inhibits sost expression by deacetylating histone 3 at its promoter. We asked whether a Sirt1-activating compound could rescue ovariectomy (OVX)-induced bone loss and biomechanical deterioration in 9-week-old C57BL/6 mice. OVX resulted in a substantial decrease in skeletal Sirt1 expression accompanied by an increase in sclerostin. Oral administration of SRT3025, a Sirt1 activator, at 50 and 100 mg/kg·d for 6 weeks starting 6 weeks after OVX fully reversed the deleterious effects of OVX on vertebral bone mass, microarchitecture, and femoral biomechanical properties. Treatment with SRT3025 decreased bone sclerostin expression and increased cortical periosteal mineralizing surface and serum propeptide of type I procollagen, a bone formation marker. In vitro, in the murine long bone osteocyte-Y4 osteocyte-like cell line SRT3025 down-regulated sclerostin and inactive β-catenin, whereas a reciprocal effect was observed with EX-527, a Sirt1 inhibitor. Sirt1 activation by Sirt1-activating compounds is a potential novel pathway to down-regulate sclerostin and design anabolic therapies for osteoporosis concurrently ameliorating other metabolic and age-associated conditions.

Genetic influence on bone turnover in postmenopausal twins.

Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone loss is likely to be small.