Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cbfβ Is a Novel Modulator Against Osteoarthritis by Maintaining Articular Cartilage Homeostasis Through TGF-Ꞵ Signaling

Xiangguo Che
† ORCID logo ,
Xian Jin
† ORCID logo ,
Narae Park
ORCID logo ,
Hee-June Kim
,
Hee-Soo Kyung
,
Hyun-Ju Kim
,
Jane B. Lian
,
Janet L. Stein
,
And Je-Yong Choi
* ORCID logo
†
These authors contributed equally to this work.
Version 1 : Received: 14 February 2023 / Approved: 16 February 2023 / Online: 16 February 2023 (09:40:30 CET)

A peer-reviewed article of this Preprint also exists.

Che, X.; Jin, X.; Park, N.R.; Kim, H.-J.; Kyung, H.-S.; Kim, H.-J.; Lian, J.B.; Stein, J.L.; Stein, G.S.; Choi, J.-Y. Cbfβ Is a Novel Modulator against Osteoarthritis by Maintaining Articular Cartilage Homeostasis through TGF-β Signaling. Cells 2023, 12, 1064. Che, X.; Jin, X.; Park, N.R.; Kim, H.-J.; Kyung, H.-S.; Kim, H.-J.; Lian, J.B.; Stein, J.L.; Stein, G.S.; Choi, J.-Y. Cbfβ Is a Novel Modulator against Osteoarthritis by Maintaining Articular Cartilage Homeostasis through TGF-β Signaling. Cells 2023, 12, 1064.

Abstract

TGF-ꞵ signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-ꞵ signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor β (Cbfβ) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbfβ in maintaining articular cartilage remains obscure. This study investigated Cbfβ as a novel anabolic modulator of TGF-ꞵsignaling and determined its role in articular cartilage homeostasis. Cbfβ significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb△ac/△ac) exhibited early cartilage degeneration at 20 weeks old and developed OA at 12 months old. Cbfb△ac/△ac mice showed enhanced OA progression under the surgical-induced mice OA model. Mechanistically, forced expression of Cbfβ rescued Col2α1 and Runx1 expression in Cbfβ-deficient chondrocytes. TGF-ꞵ1-mediated Col2α1 expression failed despite the pSmad3 activation under TGF-ꞵ1 treatment in Cbfβ-deficient chondrocytes. Cbfβ protected Runx1 from proteasomal degradation through Cbfβ/Runx1 complex formation. These results indicate that Cbfβ is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbfβ could protect OA development by maintaining the integrity of the TGF-ꞵ1 signaling pathway in articular cartilage.

Keywords

articular cartilage; Runx1/Cbfβ complex; Osteoarthritis; TGF-β signaling; proteasomal degradation

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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