Volume 38, Issue 7 e23594
RESEARCH ARTICLE

Hypobaric hypoxia aggravates osteoarthritis via the alteration of the oxygen environment and bone remodeling in the subchondral zone

Qianhao Li

Qianhao Li

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China

Search for more papers by this author
Zhouyuan Yang

Zhouyuan Yang

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China

Search for more papers by this author
Mengli Zhu

Mengli Zhu

Research Core Facility, West China Hospital, Sichuan University, Chengdu, China

Search for more papers by this author
Wanli Zhang

Wanli Zhang

Research Core Facility, West China Hospital, Sichuan University, Chengdu, China

Search for more papers by this author
Liyile Chen

Liyile Chen

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China

Search for more papers by this author
Hongying Chen

Corresponding Author

Hongying Chen

Research Core Facility, West China Hospital, Sichuan University, Chengdu, China

Correspondence

Pengde Kang, Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.

Email: [email protected]

Hongying Chen, Research Core Facility, West China Hospital, Sichuan University, Chengdu, China.

Email: [email protected]

Search for more papers by this author
Pengde Kang

Corresponding Author

Pengde Kang

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China

Correspondence

Pengde Kang, Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.

Email: [email protected]

Hongying Chen, Research Core Facility, West China Hospital, Sichuan University, Chengdu, China.

Email: [email protected]

Search for more papers by this author
First published: 04 April 2024

Qianhao Li, Zhouyuan Yang and Mengli Zhu contributed equally to this work and should be regarded as co-first authors.

Abstract

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high-altitude environment. Micro-computed tomography (Micro-CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co-culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH-OA group compared to that in the normoxia-OA (N-OA) group, 4 weeks after surgery. Micro-CT analysis revealed more deteriorated bone mass in the HH-OA group than in the N-OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH-OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co-culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH-OA group. HH-related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.

DATA AVAILABILITY STATEMENT

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.