Associations of osteoclastogenesis and nerve growth in subchondral bone marrow lesions with clinical symptoms in knee osteoarthritis

Feng Zhou; Xuequan Han; Liao Wang; Weituo Zhang; Junqi Cui; Zihao He; Kai Xie; Xu Jiang; Jingke Du; Songtao Ai; Qi Sun; Haishan Wu; Zhifeng Yu; Mengning Yan

doi:10.1016/j.jot.2021.11.002

Associations of osteoclastogenesis and nerve growth in subchondral bone marrow lesions with clinical symptoms in knee osteoarthritis

J Orthop Translat. 2021 Dec 1:32:69-76. doi: 10.1016/j.jot.2021.11.002. eCollection 2022 Jan.

Authors

Feng Zhou^{1

2}, Xuequan Han^{1

3}, Liao Wang¹, Weituo Zhang⁴, Junqi Cui⁵, Zihao He¹, Kai Xie¹, Xu Jiang¹, Jingke Du¹, Songtao Ai⁶, Qi Sun⁶, Haishan Wu¹, Zhifeng Yu¹, Mengning Yan¹

Affiliations

¹ Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
³ Department of Orthopaedics, Qilu Hospital, Shandong University, Shandong University Center for Orthopaedics, Shandong University, Jinan, China.
⁴ Clinical Research Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background/objective: Subchondral bone marrow lesions (BMLs) are common magnetic resonance imaging (MRI) features in joints affected by osteoarthritis (OA), however, their clinical impacts and mechanisms remain controversial. Thus, we aimed to investigate subchondral BMLs in knee OA patients who underwent total knee arthroplasty (TKA), then evaluate the associations of osteoclastogenesis and nerve growth in subchondral BMLs with clinical symptoms.

Methods: Total 70 patients with primary symptomatic knee OA were involved, then separated into three groups based on MRI (without BMLs group, n = 14; BMLs without cyst group, n = 37; BMLs with cyst group, n = 19). Volume of BMLs and cyst-like lesions was calculated via the OsiriX system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to assess clinical symptoms. Histology and immunohistochemistry were deployed to assess subchondral osteoclastogenesis and nerve distribution. Pearson's correlation coefficient was used to evaluate the associations between volume of BMLs and joint symptoms, and to assess the associations of osteoclastogenesis and nerve growth in subchondral BMLs with joint symptoms.

Results: In BMLs combined with cyst group, patients exhibited increased osteoclastogenesis and nerve distribution in subchondral bone, as shown by increased expression of tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5). Volume of subchondral cyst-like component was associated with joint pain (p < 0.05). Subchondral osteoclastogenesis and nerve distribution were positively associated with joint pain in BMLs with cyst group (p < 0.05).

Conclusion: The subchondral cyst-like lesion was an independent factor for inducing pain in OA patients; osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for this joint pain.

The translational potential of this article: Our results indicated that the increased osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for the pain of OA joints. These findings may provide valuable basis for the treatment of OA.

Keywords: Bone marrow lesions; Cyst-like lesions; Knee osteoarthritis; Nerve growth; Osteoclastogenesis.