Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration.

Abstract

The degeneration of articular cartilage is a key feature of osteoarthritis (OA)'. It is characterized by a loss of the tensile strength (1-3) of this tissue. The incidence of OA increases progressively with age (4). This is in association with a progressive reduction in tensile properties during aging (5). Whereas the large aggregating proteoglycan (now called aggrecan) is responsible for the compressive stiffness of cartilage (6, 7), it is the collagen fibrillar network that determines the tensile properties of this tissue ( 1, 2). These collagen fibrils are primarily composed of type H collagen (-90-95%) but also contain type IX collagen, covalently bound to type II, and type XI collagen which together comprise 2-4% of the total collagen (8).These biomechanical changes are indicative of damage to the collagen fibrils in aging and OA. To investigate these changes at the molecular level first polyclonal (9) and then monoclonal (10) antibodies were developed that only react with epitopes on the collagen a, (II) chains when the triple helix has been denatured, such as occurs following cleavage by interstitial collagenase (MMP1) which results in unwinding of the triple helix.Using a monoclonal antibody in an immunoassay, quantitative evidence was obtained to indicate that there is indeed increased denaturation of type II collagen in osteoarthritic cartilage (10). In the study presented here we describe the use of this antibody to determine where, in both aging and osteoarthritis, this damage to type II collagen occurs. We show that it starts at the articular surface and spreads into the mid and deep zones with increasing degeneration, denaturation being first observed around chondrocytes implicating these cells as primary mediators of collagen degradation in aging and OA. Tissue. Full depth human articular femoral condylar cartilages (0.5-1.0 cm2 surface area) were removed within 15 h of death with a sharp scalpel from the anterior loaded regions of the adult knee joint from a total of 11 individuals, of various ages and sexes, with no observable arthritic joint abnormalities nor recent (2-3 mo) chemotherapy (see Table I). A total of 51 patients underwent total knee arthroplasty for osteoarthritis diagnosed using the criteria of the American College of Rheumatology. Site matched femoral condylar cartilages that remained were immediately removed to the laboratory. By definition, osteophytic cartilages were excluded from this study. Single samples from 30 patients (see Table I) and 12 multiple samples from three other patients 1. Abbreviation used in this paper: OA, osteoarthritis. MethodsType II Collagen Denaturation 2859 J. Clin. Invest.

Effect of multislice acquisition on T1 and T2 measurements of articular cartilage at 3T

“…Again, our observation is in good agreement with those of previous studies (31). Generally, degeneration of cartilage will progress from the surface of the cartilage (34). Thus, the susceptibility to MT in cartilage will decrease more in the superficial layer than in the deep layer, and this difference may lead to an over-estimation of cartilage degeneration.…”

“…A total of 10 knees were involved in the T 1 measurement study (three men, two women), and the other 10 knees were involved in the T 2 measurement study (three men, two women). Mean age at time of imaging was 31.8 Ϯ 3.9 years [25][26][27][28][29][30][31][32][33][34][35][36] (values are given throughout as mean Ϯ SD [range]) for the T 1 measurement study and 29.5 Ϯ 4.9 years [24 -36] for the T 2 measurement study. Exclusion criteria were history of knee pain or abnormality or trauma of the knee joint requiring medical treatment.…”

The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis

“…This strongly suggests that the activation of potential proteolytic degradation pathways of CII after a joint injury occurs as rapidly as that for aggrecan and other cartilage matrix components. This observation corroborates and extends recent studies by other techniques that have provided evidence for early damage to the cartilage collagen network after joint injury and in OA (26,(32)(33)(34)(35)51).…”

“…4). However, recent studies have called this concept into question by providing evidence that cartilage collagen may be an early site of damage in the disease process initiated by joint trauma and OA, as well as in inflammatory arthritides (26,(32)(33)(34)(35)(36). Therefore, the aim of the present study was to quantify a neoepitope specific to the crosslinked C-telopeptide domain of CII in SF from patients with knee joint injury, OA, or other knee arthritides.…”

Early changes in serum type ii collagen biomarkers predict radiographic progression at one year in inflammatory arthritis patients after biologic therapy

“…Type II collagen (CII) is the main collagen of articular cartilage, and CII is excessively degraded in RA, PsA, and osteoarthritis (OA) (20)(21)(22)(23)(24)(25), an effect believed to result from its cleavage by collagenases. Cleavage of the triple helix of CII by collagenase exposes a helical neoepitope Col2-3/4C long mono (C2C), which can be detected by immunoassay (26)(27)(28).…”