Targeting EFEMP1 Enhances Chondrogenesis and Inhibits Hypertrophic Differentiation in a Spontaneous Osteoarthritis Mouse Model — ASN Events
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  3. Targeting EFEMP1 Enhances Chondrogenesis and Inhibits Hypertrophic Differentiation in a Spontaneous Osteoarthritis Mouse Model

Targeting EFEMP1 Enhances Chondrogenesis and Inhibits Hypertrophic Differentiation in a Spontaneous Osteoarthritis Mouse Model (#222)

Mei-Feng Chen 1 , Pei-Heng Jiang 1 , Yung-Heng Hsu 1 2 , Chih-Chien Hu 1 2 , Steve Wen-Neng Ueng 1 2 , Yuhan Chang 1 2
  1. Bone and Joint Research Center, Chang Gung Memorial Hospital, LINKOU Branch, Taoyuan County, Taiwan, Taoyuan City, N/A, Taiwan
  2. Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage degradation. EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) has been implicated in cartilage development and OA pathogenesis, as its expression inhibits chondrogenesis and declines during mesenchymal stem cell differentiation. This study aimed to investigate the role of EFEMP1 in cartilage regulation and evaluate the therapeutic potential of EFEMP1 inhibition in OA. EFEMP1 knockdown mediated by small interfering RNA (siRNA) was performed in human chondrocyte and mouse pre-osteoblast cultures. In chondrocytes, EFEMP1 knockdown downregulated hypertrophic markers (MMP-13, COL10A1) and upregulated SOX9 and aggrecan. Furthermore, phosphokinase analysis revealed increased activities of p70S6K, β-catenin, and HSP60. In osteoblasts, EFEMP1 knockdown reduced RUNX2 expression, calcification, and ALP activity. In vivo, STR/ort spontaneous OA mice were treated with EFEMP1-neutralizing antibody to assess cartilage preservation and cytokine modulation. As a result, EFEMP1 antibody treatment increased matrix-producing chondrocytes, improved cartilage integrity, and lowered OARSI scores. It also enhanced SOX9 and COL2A1 expression while suppressing COL10A1. Although no significant changes were observed in subchondral bone parameters, cytokine analysis revealed a chondroprotective effect in the EFEMP1 antibody-treated group. In conclusion, EFEMP1 inhibition promotes chondrogenesis, suppresses chondrocyte hypertrophy, and modulates inflammatory signaling, contributing to cartilage preservation and attenuation of OA progression. These findings identify EFEMP1 as a potential therapeutic target for OA.

 

Keywords：Osteoarthritis (OA); EFEMP1 (fibulin-3); Cartilage homeostasis; Chondrocyte differentiation; Extracellular matrix (ECM); STR/ort mouse model