Human osteoarthritis cartilage-derived stromal cells activate joint degeneration through TGF-beta lateral signaling.
FASEB J
; 34(12): 16552-16566, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33118211
ABSTRACT
Human osteoarthritis cartilage contains chondrocytes (OAC) and mesenchymal stromal cells (OA-MSC). Here, we found that TGF-ß 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-ß) Receptor-1. While TGF-ß specifically activated SMAD2 in OAC, it also activated BMP signaling-associated SMAD1 in OA-MSC. While TGF-ß stimulated chondrogenesis in OAC, it induced hypertrophy, mineralization, and MMP-13 in OA-MSC. Inhibiting TGF-ßR1 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.
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Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
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Transdução de Sinais
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Cartilagem Articular
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Fator de Crescimento Transformador beta
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Células-Tronco Mesenquimais
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article