Lower androgen levels promote abnormal cartilage development in female patients with adolescent idiopathic scoliosis

Yuan-Tao Wu; Ming-Xing Tang; Yun-Jia Wang; Jiong Li; Yu-Xiang Wang; Ang Deng; Chao-Feng Guo; Hong-Qi Zhang

doi:10.21037/atm-20-3171

Lower androgen levels promote abnormal cartilage development in female patients with adolescent idiopathic scoliosis

Ann Transl Med. 2021 May;9(9):784. doi: 10.21037/atm-20-3171.

Authors

Yuan-Tao Wu^{1

2

3}, Ming-Xing Tang^{1

2}, Yun-Jia Wang^{1

2}, Jiong Li^{1

2}, Yu-Xiang Wang^{1

2}, Ang Deng^{1

2}, Chao-Feng Guo^{1

2}, Hong-Qi Zhang^{1

2}

Affiliations

¹ Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Spine Surgery, Hainan General Hospital and Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.

Abstract

Background: Adolescent idiopathic scoliosis (AIS) is a disease characterized by changes in the three-dimensional structure of the spine. Studies have shown that the development of AIS might be associated with genetic, biomechanics, endocrine factors and abnormal bone or cartilage development.

Methods: Blood samples collected from 301 female patients (161 females with AIS and 140 females without AIS) were used for genotyping. Forty-eight serum samples from 161 females with AIS and 40 serum samples from 140 females without AIS were subjected to enzyme-linked immunosorbent assays (ELISAs). We also evaluated 32 facet joints (18 females with AIS and 14 females without AIS from the 301 female patients) using immunohistochemistry, Western blotting, and isolation of human primary chondrocytes, among other methods. We treated the AIS primary chondrocytes with dihydrotestosterone (DHT) to verify the relationship among androgen, the androgen receptor (AR), and its downstream pathway proteins.

Results: The serum androgen level in the AIS group was significantly decreased (1.94±0.09 vs. 2.284±0.103) compared with that in the non-AIS (control) group. The single nucleotide polymorphism genotyping results showed that the mutation rates of rs6259 between the AIS and control groups were significantly different (G/G genotype: 48.4% vs. 42.1%, G/A genotype: 40.4% vs. 35.7%, P<0.05). The levels of interleukin (IL)-6 and metalloproteinase (MMP)-13 were increased in the cartilage of AIS patients, and these patients also exhibited decreased AR levels. The cell experiment results showed that androgen reduced the degree of abnormal cartilage development in female AIS patients through the AR/IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway.

Conclusions: Our study provides a new perspective on the pathogenesis of AIS and indicates that decreased androgen levels in female AIS patients play a potential role in the development of AIS via the AR/IL-6/STAT3 signaling pathway.

Keywords: Adolescent idiopathic scoliosis (AIS); androgen; cartilage; interleukin (IL)-6; signal transducer and activator of transcription 3 (STAT3).