Identification of osteoblastic autophagy-related genes for predicting diagnostic markers in osteoarthritis
Rulong Cai,
Qijun Jiang,
Dongli Chen,
Qi Feng,
Xinzhi Liang,
Zhaoming Ouyang,
Weijian Liao,
Rongkai Zhang,
Hang Fang
Affiliations
Rulong Cai
Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China; Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China; Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
Qijun Jiang
The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China; Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China
Dongli Chen
Department of Ultrasound, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518053, China
Qi Feng
Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China; Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China; Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
Xinzhi Liang
Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China; Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China; Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
Zhaoming Ouyang
Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China; Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China; Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
Weijian Liao
Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China; Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China; Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
Rongkai Zhang
Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China; Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China; Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China; Corresponding author
Hang Fang
Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, China; Academy of Orthopedics · Guangdong Province, Guangzhou, 510630, China; Orthopedic Hospital of Guangdong Province, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China; Corresponding author
Summary: The development of osteoarthritis (OA) involves subchondral bone lesions, but the role of osteoblastic autophagy-related genes (ARGs) in osteoarthritis is unclear. Through integrated analysis of single-cell dataset, Bulk RNA dataset, and 367 ARGs extracted from GeneCards, 40 ARGs were found. By employing multiple machine learning algorithms and PPI networks, three key genes (DDIT3, JUN, and VEGFA) were identified. Then the RF model constructed from these genes indicated great potential as a diagnostic tool. Furthermore, the model’s effectiveness in predicting OA has been confirmed through external validation datasets. Moreover, the expression of ARGs was examined in osteoblasts subject to excessive mechanical stress, human and mouse tissues. Finally, the role of ARGs in OA was confirmed through co-culturing explants and osteoblasts. Thus, osteoblastic ARGs could be crucial in OA development, providing potential diagnostic and treatment strategies.
