Pain prediction by serum biomarkers of bone turnover in people with knee osteoarthritis: an observational study of TRAcP5b and cathepsin K in OA

Abstract

(2017) Pain prediction by serum biomarkers of bone turnover in people with knee osteoarthritis: an observational study of TRAcP5b and cathepsin K in OA. Osteoarthritis and Cartilage, 25 (6). pp. 858-865. ISSN 1522-9653 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/40543/1/1-s2.0-S1063458417300092-main_accepted %20manuscript%20copy.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Two putative osteoclast biomarkers were measured in sera: TRAcP5b and cathepsin K. 30Medial tibia plateaux were donated at knee arthroplasty for symptomatic OA (n=84) or from Results 35Serum TRAcP5b activity, but not cathepsin K-immunoreactivity, was associated with density 36 of TRAcP-positive osteoclasts in the subchondral bone of medial tibia plateaux. TRAcP-37 positive osteoclasts were more abundant in people with symptomatic OA compared to 38 controls. Serum TRAcP5b activity was associated with baseline pain and pain change.

Associations of Symptomatic Knee Osteoarthritis With Histopathologic Features in Subchondral Bone

“…Classification of cases as symptomatic or asymptomatic was significantly predicted by NGF immunoreactivity but not by subchondral trabecular bone density. Our current results therefore extend findings from a previous study , which demonstrated the potential role of increased osteoclast density in subchondral bone in the generation of OA pain. High serum concentrations of TRAP‐5b, an indicator of osteoclast number, were shown to be associated with subchondral osteoclast density, OA pain, and worse pain prognosis .…”

“…Differentiated osteoclasts were identified by TRAP staining, using a commercially available kit (#386A; Sigma‐Aldrich) according to the manufacturer's protocol. TRAP‐positive osteoclasts were counted within 400 μm of the cement line in the osteochondral junction and divided by the length of the subchondral bone to give an osteoclast density expressed as TRAP‐positive/mm . One dark‐purplish or reddish cell with ≥3 nuclei was recorded as 1 osteoclast.…”

“…In human OA, NGF is up‐regulated in synovium and subchondral bone , and increased synovial NGF expression was associated with symptomatic knee OA , although the relevance of subchondral NGF expression has not been clarified. Increased density of tartrate‐resistant acid phosphatase (TRAP)–positive osteoclasts in subchondral bone has also been shown to be associated with OA and knee symptoms . Inflammatory CD68‐positive macrophages were also detected in subchondral bone marrow compartments in human OA .…”

Synovial fluid pro-inflammatory profile differs according to the characteristics of knee pain

“…Recently, tartrate resistant acid phosphatase 5b (TRAcP5b), which was shown to be associated with the density and number of TRAcP-positive osteoclasts in subchondral bone, was statistically significantly associated with OA pain and change in pain (42). This in future could be a promising candidate to assess for association with OA Although previous studies have identified associations of pro-inflammatory cytokines with cartilage destruction, subchondral bone remodeling, synovial inflammation (7,11), and OA severity and progression (43)(44)(45), only a limited number of studies have reported correlations of sf IL-6, IL-8 and TNFα to levels of pain.…”

Blood Transcriptional Signatures for Disease Progression in a Rat Model of Osteoarthritis

“…It is characterized by progressive loss of function in the synovial joints. There are a variety of factors that play an important role in the pathogenesis of OA, including biomechanical factors, proinflammatory mediators, and proteases [1–4]. The primary symptoms of OA are joint pain, stiffness, and locomotor restriction.…”