2. Academic Validation
  3. Single-cell atlas of human infrapatellar fat pad and synovium implicates APOE signaling in osteoarthritis pathology

Single-cell atlas of human infrapatellar fat pad and synovium implicates APOE signaling in osteoarthritis pathology

  • Sci Transl Med. 2024 Jan 24;16(731):eadf4590. doi: 10.1126/scitranslmed.adf4590.
Su'an Tang 1 2,  Lutian Yao 3,  Jianzhao Ruan 1,  Jingliang Kang 1,  Yumei Cao 1,  Xiaoyu Nie 1,  Weiren Lan 1,  Zhaohua Zhu 1,  Weiyu Han 1 2,  Yongguang Liu 4,  Jing Tian 2,  Patrick Seale 5,  Ling Qin 6,  Changhai Ding 1 7
Affiliations

Affiliations

  • 1 Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
  • 2 Centre of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
  • 3 Department of Orthopaedic Surgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
  • 4 Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
  • 5 Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 6 Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 7 Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, Australia.
PMID: 38266107 DOI: 10.1126/scitranslmed.adf4590
Abstract

The infrapatellar fat pad (IPFP) and synovium play essential roles in maintaining knee joint homeostasis and in the progression of osteoarthritis (OA). The cellular and transcriptional mechanisms regulating the function of these specialized tissues under healthy and diseased conditions are largely unknown. Here, single-cell and single-nuclei RNA sequencing of human IPFP and synovial tissues were performed to elucidate the cellular composition and transcriptional profile. Computational trajectory analysis revealed that Dipeptidyl Peptidase 4+ mesenchymal cells function as a common progenitor for IPFP adipocytes and synovial lining layer fibroblasts, suggesting that IPFP and synovium represent an integrated tissue unit. OA induced a profibrotic and inflammatory phenotype in mesenchymal lineage cells with biglycan+ intermediate fibroblasts as a major contributor to OA fibrosis. Apolipoprotein E (APOE) signaling from intermediate fibroblasts and macrophages was identified as a critical regulatory factor. Ex vivo incubation of human cartilage with soluble APOE accelerated proteoglycan degeneration. Inhibition of APOE signaling by intra-articular injection of an anti-APOE neutralizing antibody attenuated the progression of collagenase-induced OA in mice, demonstrating a detrimental effect of APOE on cartilage. Our studies provide a framework for designing further therapeutic strategies for OA by describing the cellular and transcriptional landscape of human IPFP and synovium in healthy versus OA joints.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z