Intermittent intra-articular delivery of FGF8b enhances cartilage homeostasis and attenuates osteoarthritis progression

Xiuqin Peng; Jiaming Han; Yu Tian; Xiaohong Li; Xuanqi Zhang; Song Li; Jun Yang; Liang Chen; Siru Zhou; Nan Su; Xueqin Mao; Bin Zhang; Hangang Chen; Jing Yang; Min Jin; Can Li; Wanling Jiang; Peng Liu; Yangli Xie; Liang Kuang; Lin Chen

doi:10.1016/j.jot.2025.101037

Intermittent intra-articular delivery of FGF8b enhances cartilage homeostasis and attenuates osteoarthritis progression

J Orthop Translat. 2026 Jan 13:56:101037. doi: 10.1016/j.jot.2025.101037. eCollection 2026 Jan.

Authors

Xiuqin Peng^{1

2}, Jiaming Han^{1

2}, Yu Tian², Xiaohong Li², Xuanqi Zhang³, Song Li², Jun Yang², Liang Chen⁴, Siru Zhou⁵, Nan Su², Xueqin Mao², Bin Zhang², Hangang Chen², Jing Yang², Min Jin², Can Li², Wanling Jiang⁶, Peng Liu⁷, Yangli Xie², Liang Kuang², Lin Chen^{1

2}

Affiliations

¹ Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China.
² Center of Bone Metabolism and Repair, Laboratory for Prevention and Rehabilitation of Military Training Injuries, State Key Laboratory of Trauma and Chemical Poisoning, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China.
³ Wenzhou Medical University, Wenzhou, 325035, China.
⁴ Department of Orthopedic, Daping Hospital, Army Medical University, Chongqing, 400042, China.
⁵ War Trauma Medical Center, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical Center, Daping Hospital, Army Medical University, Chongqing, 40038, China.
⁶ Department of Chinese Traditional Medicine and Rehabilitation, Chongqing Emergency Medical Center (Chongqing University Central Hospital), Chongqing, 400014, China.
⁷ Department of Spine Surgery, Center of Orthopedics, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, China.

Abstract

Objective: Osteoarthritis (OA) is a chronic disease characterized by degeneration of articular cartilage, affecting over half a billion individuals globally. Current treatments such as non-steroidal anti-inflammatory drugs are effective in symptom relief, but lack the ability to modify OA progression. Fibroblast growth factor 8b (FGF8b) plays crucial roles in chondrogenesis and cartilage formation, suggesting its potential application in cartilage homeostasis maintenance. This study aims to investigate the effect of exogenous FGF8b on cartilage protection and OA progression, and explore the underlying mechanisms.

Design: Therapeutic effects of intra-articular FGF8b injections either once weekly or once every four weeks were evaluated in OA mouse models induced by destabilization of the medial meniscus (DMM) using histological analysis, X-ray imaging, micro-computed tomography (micro-CT), immunohistochemistry (IHC), and RNA sequencing of cartilage. Additionally, the therapeutic effects and underlying mechanisms of FGF8b on human cartilage and chondrocytes were further investigated using ex vivo OA models and in vitro assays.

Results: Once-weekly administration of FGF8b attenuated cartilage degradation while exacerbating osteophyte formation in a dose-dependent manner. Higher doses of FGF8b resulted in stronger cartilage-protective effects while increased osteophyte formation. Conversely, intermittent administration of FGF8b (once every four weeks) protected cartilage from degeneration without causing significant osteophyte formation. Mechanistically, FGF8b was found to help the maintenance of cartilage homeostasis by promoting anabolic metabolism and inhibiting catabolic metabolism in chondrocytes through activation of the FGFR3-PI3K-AKT signaling pathway.

Conclusions: Exogenous FGF8b attenuates articular cartilage degeneration by increasing anabolism and inhibiting catabolism, thereby presenting therapeutic potential for OA treatment.

The translational potential of this article: In this study, we demonstrate that intermittent administration of FGF8b protects articular cartilage from degeneration by increasing anabolic metabolism and inhibiting catabolic metabolism in cartilage, making it a promising disease-modifying agent for OA. Moreover, the findings offer valuable insights into optimizing the exposure regimens of FGFs to achieve safer and more effective OA treatment.

Keywords: Articular cartilage; Cartilage homeostasis; Chondrocyte; FGF8b; Osteoarthritis; Osteophyte.