Uncoupling of collagen II metabolism in newly diagnosed, untreated rheumatoid arthritis is linked to inflammation and antibodies against cyclic citrullinated peptides.

Objective: To investigate the relationship between markers of collagen II synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naïve to disease-modifying antirheumatic drugs.

Methods: One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years.

Structures of strontium diformate and strontium fumarate. A synchrotron powder diffraction study.

The crystal structures of strontium diformate in space groups P2(1)2(1)2(1) (alpha form, 295 K), P4(1)2(1)2 (beta form, 334 and 540 K) and I4(1)/amd (delta form, 605 K), and strontium fumarate in space groups Fddd (beta form, 105 K) and I4(1)/amd (alpha form, 293 K) have been determined from synchrotron X-ray powder diffraction data. Except for the alpha-strontium diformate, all the structures are based on a diamond-like Sr-ion arrangement, as in strontium acetylene dicarboxylate. The formate ions are disordered in the delta phase owing to steric hindrance.

Differential association of the N-propeptide of collagen IIA (PIIANP) and collagen II C-telopeptide (CTX-II) with synovitis and erosions in early and longstanding rheumatoid arthritis.

Objectives: To determine the N-terminal propeptide of collagen IIA (PIIANP) in early and established rheumatoid arthritis (RA) and to study the association with collagen II degradation assessed by its C-telopeptide (CTX-II), x-ray status and disease activity measures.

Methods: Two cohorts of RA patients were included: A) a one-year prospective cohort including 45 patients with early, untreated RA and B) a cross-sectional study comprising 50 RA patients with advanced disease. Blood donors and healthy volunteers served as controls.

Posttranslational Protein Modifications in Type 1 Diabetes - Genetic Studies with PCMT1, the Repair Enzyme Protein Isoaspartate Methyltransferase (PIMT) Encoding Gene.

Background: Posttranslational protein modifications have been implicated in the development of autoimmunity. Protein L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) repairs modified proteins and is encoded by PCMT1, located in a region linked to type 1 diabetes (T1D), namely IDDM5.

Aim: To evaluate the association between genetic variations in the PCMT1 gene and T1D.

Application of inductively coupled plasma-mass spectrometry (ICP-MS) and quality assurance to study the incorporation of strontium into bone, bone marrow, and teeth of dogs after one month of treatment with strontium malonate.

The strontium content of serum, bone, marrow, and teeth was determined by inductively-coupled plasma mass spectrometry (ICP-MS). Significant correlations were obtained after the data were subjected to quality assurance (QA) performed according to validated procedures. After four weeks of treatment with strontium malonate, strontium levels increased from 76 +/- 9 microg g(-1) in placebo-treated dogs to levels of 7.

Urinary markers of altered collagen metabolism in fibromyalgia patients.

Objective: To assess the metabolism of collagen in fibromyalgia (FM) patients, and to compare the occurrence of collagen metabolism markers to the severity of FM symptoms.

Methods: Morning urine was collected from 27 FM women fulfilling the American College of Rheumatology (ACR) criteria for FM, and from seven controls. FM patients completed the Fibromyalgia Impact Questionnaire (FIQ).

Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?

Aims/hypothesis: Post-translational modifications, such as isomerisation of native proteins, may create new antigenic epitopes and play a role in the development of the autoimmune response. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), encoded by the gene PCMT1, is an enzyme that recognises and repairs isomerised Asn and Asp residues in proteins. The aim of this study was to assess the role of PIMT in the development of type 1 diabetes.

Sex hormones in the regulation of bone and cartilage metabolism: an old paradigm and a new challenge.

The effects of estrogen on tissues such as bone, endometrium and breast have been extensively studied, and the pleitropic effects of the female sex hormone are well established. Cartilage is not generally viewed as an estrogen responsive tissue. However, several epidemiological studies, and a few recent intervention studies supports that estrogen may have a role in osteoarthritis (OA), and recent animal studies further suggests that estrogen may be involved in regulation of cartilage turnover.

Strontium D-glutamate hexahydrate and strontium di(hydrogen L-glutamate) pentahydrate.

[Sr(C5H7NO4)].6H2O, (I), and [Sr(C5H8NO4)2].5H2O, (II), both crystallize with similar strontium-glutamate-water layers.

New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis.

Objective: Protein nitration is a prominent feature of inflammatory processes in the joint. We have developed immunoassays specific for a peptide of the alpha-helical region of type II collagen 108HRGYPGLDG116 (Coll 2-1) and its nitrated form 108HRGY(NO2)PGLDG116 (Coll 2-1 NO2) in biological fluids.

Design: Coll 2-1 and Coll 2-1 NO2 peptides were injected into rabbits.

The effect on cartilage of different forms of application of postmenopausal estrogen therapy: comparison of oral and transdermal therapy.

The effect on urine C-telopeptides of type II collagen (uCTX-II) of oral and transdermal estradiol treatment was compared using samples from two randomized, double-blind, placebo-controlled trials. A total of 171 healthy, Danish postmenopausal women, 45-65 years of age completed the 2-year study periods. The uCTX-II marker assessed cartilage degradation, and this response was compared with the effect on urine C-telopeptides of type I collagen (uCTX-I), considered a specific marker of bone resorption.

Characterization of aged osteocalcin fragments derived from bone resorption.

Introduction: Osteocalcin (OC) is a small bone matrix protein exclusively found in mineralized tissue. OC measured in serum or plasma provides an index of bone formation. In the present study a sensitive inhibition ELISA was established that could quantify fragments derived from the OC Mid-region in human urine.

Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456].

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years.

Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM).

Objective: Several observational studies indicate that estrogen deficiency increases the incidence of osteoarthritis in postmenopausal women. To validate this observation, we investigated the effects of ovariectomy (OVX) on cartilage erosion in rats using histology and an established bio-assay of cartilage-specific collagen type II degradation products (CTX-II). Furthermore, we investigated whether estrogen and levormeloxifene, a selective estrogen-receptor modulator (SERM), can prevent the OVX-induced changes in cartilage degradation.

A new marker for osteoarthritis: cross-sectional and longitudinal approach.

Objective: To investigate the association between urinary concentrations of C-telopeptide fragments of type II collagen (CTX-II) and the prevalence and progression of radiographic osteoarthritis (OA) of the knee and hip.

Methods: The study population consisted of a sample of 1,235 men and women ages > or =55 years who were enrolled in the Rotterdam Study (a population-based cohort study) and who were followed up for a mean of 6.6 years.

Type II collagen peptides for measuring cartilage degradation.

This paper describes two new immunoassays for a peptide of the triple helix of type II collagen (Coll 2-1) and its nitrated form (Coll 2-1 NO(2)). In healthy subjects aged between 20 and 65 years old, Coll 2-1 and Coll 2-1 NO(2) levels in serum were in means 125.13+/-3.

An immunoassay for measuring fragments of newly synthesized collagen type I produced during metastatic invasion of bone.

Degradation products of collagen type I can be measured by CrossLaps (CTX) immunoassays, providing an index of bone resorption. The CTX epitope EKAHDGGR comprises a DG-motif susceptible to post-translational modifications. In newly synthesized collagen this motif is in the native form denoted alphaCTX, but converts to an isomerized form (betaCTX) during aging of bone.

Post-translational modifications of proteins: implications for aging, antigen recognition, and autoimmunity.

Proteins are complex organic molecules susceptible to numerous post-translational modifications occurring spontaneously during aging or as a consequence of physiologic or pathologic processes. Antigenicity and interactions of proteins with components of the immune system may be profoundly affected by post-translational modifications. Thus, modified self-antigens may be absent (not-tolerated) during early T-cell selection and trigger reactions by the immune system as they arise later in life.

Cartilage destruction in collagen induced arthritis assessed with a new biochemical marker for collagen type II C-telopeptide fragments.

Objective: To assess the ability of a marker of collagen type II degradation (CTX-II) to quantify cartilage turnover in vitro in cartilage explants and in vivo in rats with collagen induced arthritis (CIA).

Methods: Bovine articular cartilage explants were cultured in the presence of interleukin 1a, oncostatin M, and plasminogen to induce cartilage degradation. CTX-II, CTX-I (C-telopeptide fragment of collagen type I), glycosaminoglycan, and hydroxyproline contents in culture supernatants were measured.

Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application.

We aimed to assess the effect of ovariectomy on cartilage turnover and degradation, to evaluate whether ovariectomized (OVX) rats could form an experimental model of postmenopausal osteoarthritis. The effect of ovariectomy on cartilage was studied using two cohorts of female Sprague-Dawley rats, aged 5 and 7 months. In a third cohort, the effect of exogenous estrogen and a selective estrogen receptor modulator was analyzed.

Osteoarthritic patients with high cartilage turnover show increased responsiveness to the cartilage protecting effects of glucosamine sulphate.

Objective: Glucosamine sulphate has been shown in a large double-blind, placebo-controlled clinical trial to prevent structural damage and improve clinical symptoms of osteoarthritis (OA). We investigated whether early response in a newly developed biochemical marker of collagen type II degradation (CTX-II, CartiLaps ELISA) could reflect the long-term preservation of hyaline cartilage.

Methods: Study subjects comprised 212 knee OA patients participating in a clinical trial of the effects of glucosamine sulphate.

Increased urinary concentration of collagen type II C-telopeptide fragments in patients with osteoarthritis.

Objective: Osteoarthritis (OA) is characterized by a progressive degeneration of articular cartilage and loss of joint function. We hypothesized that degradation of articular cartilage results in increased fragmentation of collagen type II. Thus, the concentrations of degradation products of this major cartilage matrix protein may increase in body fluids of patients with OA.