Serum xylosyltransferase 1 level increases during early posttraumatic osteoarthritis in mice with high bone forming potential

Abstract

Increased proteoglycan (PG) synthesis is essential for the stimulation of cartilage repair processes that take place during the reversible phase of osteoarthritis (OA). In articular cartilage, xylosyltransferase 1 (Xylt1) is the key enzyme that initiates glycosaminoglycan (GAG) chain synthesis by transferring the first sugar residue to the PG core protein. Biological activity of PGs is closely linked to GAG biosynthesis since their polyanionic nature directly contributes to the proper hydration and elastic properties of the cartilage tissue present at the articular interface. The aim of this study was to investigate whether variations in the level of Xylt1 present in serum can be used to predict OA disease progression. The influence of bone forming activity on the systemic release of this enzyme was addressed by experimentally-inducing OA in mice of two different genetic backgrounds that were previously characterized for their distinct bone metabolism: C57BL/6J (B6, high bone remodelers) or C3H/HeJ (C3H, high bone formers). Serum was collected after medial meniscectomy or sham surgeries in young adult mice of these two strains over a period of 3.5 months at which point knee histopathology was assessed. A significant increase in serum Xylt1 levels observed shortly after meniscectomy positively correlated with severe cartilage damage evaluated by histological assessment at later time points in mice of the C3H background. In contrast, no temporal regulation of Xylt1 level was found between meniscectomies and control surgeries in B6 mice, which developed OA at a slower rate. Additionally, longitudinal evaluation of the serum levels of other markers of cartilage/bone metabolism (C1,2C, osteocalcin) did not reveal any association with late knee damages. Our results strongly support the idea that serum Xylt1 has a clinical value for monitoring risk of OA progression in young adults with high bone forming potential. Ultimately, the understanding of posttraumatic mechanisms regulating PG synthesis and their modification by GAG will be essential so that interventions that stimulate cartilage regrowth can be undertaken prior to irreversible destruction of the joint tissue.

Animal models of osteoarthritis: classification, update, and measurement of outcomes

“…Serum xylosyltransferase 1 ( Xylt1 ) is increased in mice models of OA under a background of mice with high bone forming potential. This study suggests an application of this marker in studying OA risk in young adults [ 297 ]. There have also been promising results in the application of biomarker research in other small animal models.…”

Pros and cons of mouse models for studying osteoarthritis

“…Another example of a commonly used strain of mice is STR/ort mice [5]. These mice have certain characteristics which [5,10,50,53] make them more likely to develop OA. For instance, they have increased levels of inflammatory cytokines including IL1β, IL12p70, MIP1β, and IL5 [12].…”

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

“…Few studies have performed correlations between different PTOA outcomes measured in the same animal, for example, between individual joint tissue changes, or between gait/pain and pathology . It is recognized that such multiple intra‐animal analyses may be restricted by the number of animals available or practical to manage within one study, the “destructive” nature of the outcome (e.g., histopathology), or multiple/repeated analysis may conflict with ethical guidelines for use of animals in research.…”