TY - JOUR
T1 - Tyrosine kinases regulate chondrocyte hypertrophy
T2 - promising drug targets for Osteoarthritis
AU - Ferrao Blanco, M. N.
AU - Domenech Garcia, H.
AU - Legeai-Mallet, L.
AU - van Osch, G. J.V.M.
PY - 2021
Y1 - 2021
N2 - Osteoarthritis (OA) is a major health problem worldwide that affects the joints and causes severe disability. It is characterized by pain and low-grade inflammation. However, the exact pathogenesis remains unknown and the therapeutic options are limited. In OA articular chondrocytes undergo a phenotypic transition becoming hypertrophic, which leads to cartilage damage, aggravating the disease. Therefore, a therapeutic agent inhibiting hypertrophy would be a promising disease-modifying drug. The therapeutic use of tyrosine kinase inhibitors has been mainly focused on oncology, but the Food and Drug Administration (FDA) approval of the Janus kinase inhibitor Tofacitinib in Rheumatoid Arthritis has broadened the applicability of these compounds to other diseases. Interestingly, tyrosine kinases have been associated with chondrocyte hypertrophy. In this review, we discuss the experimental evidence that implicates specific tyrosine kinases in signaling pathways promoting chondrocyte hypertrophy, highlighting their potential as therapeutic targets for OA.
AB - Osteoarthritis (OA) is a major health problem worldwide that affects the joints and causes severe disability. It is characterized by pain and low-grade inflammation. However, the exact pathogenesis remains unknown and the therapeutic options are limited. In OA articular chondrocytes undergo a phenotypic transition becoming hypertrophic, which leads to cartilage damage, aggravating the disease. Therefore, a therapeutic agent inhibiting hypertrophy would be a promising disease-modifying drug. The therapeutic use of tyrosine kinase inhibitors has been mainly focused on oncology, but the Food and Drug Administration (FDA) approval of the Janus kinase inhibitor Tofacitinib in Rheumatoid Arthritis has broadened the applicability of these compounds to other diseases. Interestingly, tyrosine kinases have been associated with chondrocyte hypertrophy. In this review, we discuss the experimental evidence that implicates specific tyrosine kinases in signaling pathways promoting chondrocyte hypertrophy, highlighting their potential as therapeutic targets for OA.
KW - Chondrocyte hypertrophy
KW - Disease modifying OA drugs
KW - Tyrosine kinases
UR - http://www.scopus.com/inward/record.url?scp=85111774439&partnerID=8YFLogxK
U2 - 10.1016/j.joca.2021.07.003
DO - 10.1016/j.joca.2021.07.003
M3 - Review article
AN - SCOPUS:85111774439
SN - 1063-4584
VL - 29
SP - 1389
EP - 1398
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 10
ER -