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The MAP Kinase Signaling Pathways Regulating Bone Formation
Author(s) -
Chen Qian,
Wei Lei
Publication year - 2006
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/fasebj.20.5.a868-a
Subject(s) - chondrocyte , endochondral ossification , microbiology and biotechnology , mapk/erk pathway , p38 mitogen activated protein kinases , kinase , signal transduction , medicine , muscle hypertrophy , protein kinase a , endocrinology , biology , chemistry , cartilage , anatomy
Endochondral ossification requires precise regulation and coordination of chondrocyte differentiation events that include both proliferation and hypertrophy. The failure to do so may cause chondrodysplasia. Delaying chondrocyte hypertrophy by overexpression of parathyroid hormone‐related peptide (PTH‐rP) or its constitutively active receptor, which potently inhibits chondrocyte hypertrophy, causes chondrodysplasia. So does the acceleration of chondrocyte hypertrophy by ablating the PTH/PTHrP receptor gene in mice. Therefore, controlling the pace of transition from chondrocyte proliferation to hypertrophy is essential for endochondral ossification. The mitogen‐activated protein kinase kinase 6 (MKK6) and its phosphorylation substrate p38 MAPK is part of an intracellular signaling pathway activated by proinflammatory cytokines and environmental stress. The activated p38 MAPK then phosphorylates a number of transcriptional factors thereby transmitting the signals from cytoplasm to the nucleus. We previously found that the basal level of p38 MAPK activity increased in chondrocytes from proliferating to hypertrophic, in parallel to the chondrocyte differentiation course. Furthermore, the treatment of chondrocytes with PTH(1–34), which inhibited chondrocyte hypertrophy, also decreased the p38 activity (1). In this study, we determine whether the p38 MAPK activity is involved in the regulation of chondrocyte differentiation by altering the intracellular levels of p38 MAPK activity in chondrocytes by transfection of two MAP kinase mutants with retroviral vectors, and by creating transgenic mice harboring MAP mutant. We show here that p38 MAPK is a key regulator controlling chondrocyte proliferation and hypertrophy.