Runx2, an inducer of osteoblast and chondrocyte differentiation

AbstractRunx2 is a transcription factor that is essential for osteoblast differentiation and chondrocyte maturation. Ihh, expressed in prehypertrophic and hypertrophic chondrocytes, is required for the specification of Runx2+ osteoprogenitors in endochondral bone development. Runx2 induces Sp7, an essential transcription factor for osteoblast differentiation. Canonical Wnt signaling is also required for osteoblast differentiation. Runx2+ osteoprogenitors retain the capacity to differentiate into chondrocytes, and Sp7 and canonical Wnt signaling direct cells to osteoblasts, thereby inhibiting chondrocyte differentiation. The function of Runx2 after the commitment to osteoblasts remains controversial. Runx3 has a redundant function with Runx2 in chondrocyte maturation. Runx2 regulates the expression ofIhh, Col10a1, Spp1, Ibsp, Mmp13, andVegfa in the respective layers in growth plates. Runx2 enhances chondrocyte proliferation through the induction ofIhh. Ihh induces Pthlh, which inhibits Runx2 and chondrocyte maturation, forming a negative feedback loop for chondrocyte maturation. Runx2 is one of the genes responsible for the pathogenesis of osteoarthritis (OA) because RUNX2 is up-regulated in chondrocytes in OA cartilage and a germline haplodeficiency or deletion ofRunx2 in articular chondrocytes decelerates OA progression. Runx2 plays an important role in the bone metastasis of breast and prostate cancers by up-regulatingSpp1, Ibsp, Mmp9, Mmp13, Vegfa, Tnfsf11, andIhh expressi...
Source: Histochemistry and Cell Biology - Category: Biomedical Science Source Type: research