Characteristics of gene expression in frozen shoulder

Hiroaki Nishimoto; Shoji Fukuta; Naoshi Fukui; Koichi Sairyo; Tetsuo Yamaguchi

doi:10.1186/s12891-022-05762-3

Characteristics of gene expression in frozen shoulder

BMC Musculoskelet Disord. 2022 Aug 25;23(1):811. doi: 10.1186/s12891-022-05762-3.

Authors

Hiroaki Nishimoto¹, Shoji Fukuta², Naoshi Fukui^{3

4}, Koichi Sairyo⁵, Tetsuo Yamaguchi⁶

Affiliations

¹ Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Minami-Jyosanjima 1-1, Tokushima, 770-8502, Japan.
² Department of Orthopaedic Surgery, National Hospital Organization Kochi National Hospital, Kochi, Japan.
³ Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
⁴ Clinical Research Center, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan.
⁵ Department of Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
⁶ Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Minami-Jyosanjima 1-1, Tokushima, 770-8502, Japan. t-yam@tokushima-u.ac.jp.

Abstract

Background: Severe frozen shoulder (FS) is often resistant to treatment and can thus result in long-term functional impairment. However, its etiology remains unknown. We hypothesized that gene expression of FS would vary by synovial location.

Methods: The synovial tissues of patients with FS were collected prospectively and analyzed for the expression of 19 genes. Synovial tissues from patients with rotator cuff tear (RCT) or shoulder instability (SI) were also analyzed as controls. A total of 10 samples were analyzed from each group. The specimens were arthroscopically taken from three different locations: rotator interval (RI), axillary recess (AX), and subacromial bursa (SAB). Total RNA was extracted from the collected tissues and was analyzed by real-time polymerase chain reaction for the following genes: matrix metalloproteinases (MMPs); tissue inhibitors of metalloproteinases (TIMPs); inflammatory cytokines (IL1B, TNF, and IL6); type I and II procollagen (COL1A1 and COL2A1); growth factors (IGF1 and TGFB1); neural factors (NGF and NGFR); SOX9; and ACTA2.

Results: Site-specific analysis showed that MMP13, IL-6, SOX9, and COL1A1 were increased in all three sites. Four genes (MMP3, MMP9, COL2A1, and NGFR) were increased in the AX, MMP3 in the RI, and NGFR in the SAB were increased in the FS group than in the RCT and SI groups. In the FS group, there was a correlation between the expression of genes related to chondrogenesis (MMP2, IGF1, SOX9, COL2A1, NGF, and NGFR) or fibrosis (MMP9, TGFB1, and COL1A1).

Conclusion: The expression levels of numerous MMPs, pro-inflammatory cytokines, and collagen-related genes were increased in the FS group, suggesting that catabolic and anabolic changes have simultaneously occurred. In addition, genes related to chondrogenesis or fibrosis were highly expressed in the FS group, which might have affected the range of motion limitation of the shoulder. Compared to RI and SAB, the AX was the most common site of increased expression in FS. Analyzing the lower region of the shoulder joint may lead to the elucidation of the pathogenesis of FS.

Keywords: Chondrogenesis; Fibrosis; Frozen shoulder; Gene expression.

MeSH terms

Bursitis* / genetics
Bursitis* / pathology
Cytokines / genetics
Fibrosis
Gene Expression
Humans
Joint Instability* / pathology
Matrix Metalloproteinase 3
Matrix Metalloproteinase 9
Nerve Growth Factor
Rotator Cuff Injuries* / pathology
Shoulder Joint* / pathology

Substances

Cytokines
Nerve Growth Factor
Matrix Metalloproteinase 3
Matrix Metalloproteinase 9