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Open Access Highly Accessed Research article

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis

Muneaki Ishijima123*, Taiji Watari145, Kiyohito Naito45, Haruka Kaneko12, Ippei Futami12, Kaori Yoshimura-Ishida6, Akihito Tomonaga7, Hideyo Yamaguchi6, Tetsuro Yamamoto6, Isao Nagaoka34, Hisashi Kurosawa2, Robin A Poole8 and Kazuo Kaneko123

Author affiliations

1 Department of Medicine for Motor Organ, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

2 Department of Orthopaedics, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

3 Sportology Center, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

4 Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

5 Department of Orthopaedic Surgery, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan

6 Total Technological Consultant Co., Ltd., 1-20-2, Ebisunishi, Shibuya-ku, Tokyo 150-0021, Japan

7 Tana Orthopaedic Surgery, 15-7, Tanacho, Aoba-ku Yokohama, Kanagawa 227-0064, Japan

8 Professor Emeritus, Department of Surgery, McGill University, 1650 Cedar Ave., Montreal, Quebec, H3G 1A4, Canada

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Citation and License

Arthritis Research & Therapy 2011, 13:R22  doi:10.1186/ar3246

Published: 14 February 2011

Abstract

Introduction

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.

Methods

Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA).

Results

sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.

Conclusions

These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.