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Human osteoarthritis cartilage‐derived stromal cells activate joint degeneration through TGF‐beta lateral signaling
Author(s) -
Liu Wenguang,
Feng Meng,
Jayasuriya Chathuraka T.,
Peng Hang,
Zhang Long,
Guan Yingjie,
Froehlich John A.,
Terek Richard M.,
Chen Qian
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001448r
Subject(s) - osteoarthritis , stromal cell , degeneration (medical) , cartilage , transforming growth factor beta , microbiology and biotechnology , signal transduction , tgf beta 1 , transforming growth factor , chemistry , medicine , anatomy , cancer research , pathology , biology , alternative medicine
ABSTRACT Human osteoarthritis cartilage contains chondrocytes (OAC) and mesenchymal stromal cells (OA‐MSC). Here, we found that TGF‐β had different effects on OA‐MSC and OAC, and revealed its lateral signaling mechanism in OA. RNAseq analysis indicated that OA‐MSC expressed the same level of Bone Morphogenetic Protein (BMP) Receptor‐1A as OAC but only 1/12 of Transforming Growth Factor beta (TGF‐β) Receptor‐1. While TGF‐β specifically activated SMAD2 in OAC, it also activated BMP signaling‐associated SMAD1 in OA‐MSC. While TGF‐β stimulated chondrogenesis in OAC, it induced hypertrophy, mineralization, and MMP‐13 in OA‐MSC. Inhibiting TGF‐βR1 suppressed MMP‐13 in OA‐MSC but stimulated it in OAC. In contrast, by specifically targeting BMPR1A/ACVR1 in both cell types, LDN193189 inhibits cartilage degeneration through suppressing hypertrophy and MMP‐13 in a mouse osteoarthritis model. Thus, LDN193189, a drug under development to inhibit constitutive BMP signaling during heterotopic ossification, may be re‐purposed for OA treatment.