2. Academic Validation
  3. Endothelial PDGF-BB/PDGFR-β signaling promotes osteoarthritis by enhancing angiogenesis-dependent abnormal subchondral bone formation

Endothelial PDGF-BB/PDGFR-β signaling promotes osteoarthritis by enhancing angiogenesis-dependent abnormal subchondral bone formation

  • Bone Res. 2022 Aug 29;10(1):58. doi: 10.1038/s41413-022-00229-6.
Zhuang Cui  # 1 2,  Hangtian Wu  # 3 4,  Ye Xiao  # 5 6,  Ting Xu 7,  Junjie Jia 3 4,  Hancheng Lin 3 4,  Rongmin Lin 3 4,  Kun Chen 3 4,  Yihuang Lin 3 4,  Kaiqun Li 3 4,  Xiaohu Wu 3 4,  Changjun Li 8 9,  Bin Yu 10 11
Affiliations

Affiliations

  • 1 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. [email protected].
  • 2 Guangdong Provincial Key Laboratory of Bone and Cartilage Regeneration Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. [email protected].
  • 3 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 4 Guangdong Provincial Key Laboratory of Bone and Cartilage Regeneration Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 5 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
  • 6 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China.
  • 7 Department of Sleep Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 8 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China. [email protected].
  • 9 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, 410008, China. [email protected].
  • 10 Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. [email protected].
  • 11 Guangdong Provincial Key Laboratory of Bone and Cartilage Regeneration Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 36031625 DOI: 10.1038/s41413-022-00229-6
Abstract

The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis (OA) remain unknown. No pharmacological intervention can currently prevent the progression of osteoarthritis. Accumulating evidence has shown that subchondral bone deterioration is a primary trigger for overlying cartilage degeneration. We previously found that H-type vessels modulate aberrant subchondral bone formation during the pathogenesis of OA. However, the mechanism responsible for the elevation of H-type vessels in OA is still unclear. Here, we found that PDGFR-β expression, predominantly in the CD31hiEmcnhi endothelium, was substantially elevated in subchondral bones from OA patients and rodent OA models. A mouse model of OA with deletion of PDGFR-β in endothelial cells (ECs) exhibited fewer H-type vessels, ameliorated subchondral bone deterioration and alleviated overlying cartilage degeneration. Endothelial PDGFR-β promotes angiogenesis through the formation of the PDGFR-β/talin1/FAK complex. Notably, endothelium-specific inhibition of PDGFR-β by local injection of AAV9 in subchondral bone effectively attenuated the pathogenesis of OA compared with that of the vehicle-treated controls. Based on the results from this study, targeting PDGFR-β is a novel and promising approach for the prevention or early treatment of OA.

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