ArticlePloS one2013
BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- GREM1 acts in leptin receptor-expressing skeletal cells to mediate peri-implant fibrosis.Nature communications · 2026Article
- From Osteogenesis to Diagnosis: The Role of microRNAs as Biomarkers for Osteoporosis.International journal of molecular sciences · 2026Review
- MiR-23a-5p affects postmenopausal osteoporosis by targeting ALX3 to regulate osteoblast differentiation.Journal of orthopaedic surgery and research · 2025Article
- Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms.The Journal of biological chemistry · 2021Article
- Ginsenoside Rb1 prevents steroid‑induced avascular necrosis of the femoral head through the bone morphogenetic protein‑2 and vascular endothelial growth factor pathway.Molecular medicine reports · 2019Article
- A novel hybrid compound LLP2A-alendronate accelerates open fracture healing in a rabbit model.Drug design, development and therapy · 2019Article
- TGF-β Family Signaling in Mesenchymal Differentiation.Cold Spring Harbor perspectives in biology · 2018Review
- The role of heredity in pterygium development.International journal of ophthalmology · 2014Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, while it inhibits myogenic differentiation in C2C12 cells. To evaluate genes involved in BMP-2-induced osteoblast differentiation, we performed cDNA microarray analyses to compare BMP-2-treated and -untreated C2C12 cells. We focused on Alx3 (aristaless-like homeobox 3) which was clearly induced during osteoblast differentiation. Alx3, a homeobox gene related to the Drosophilaaristaless gene, has been linked to developmental functions in craniofacial structures and limb development. However, little is known about its direct relationship with bone formation. In the present study, we focused on the mechanisms of Alx3 gene expression and function during osteoblast differentiation induced by BMP-2. In C2C12 cells, BMP-2 induced increase of Alx3 gene expression in both time- and dose-dependent manners through the BMP receptors-mediated SMAD signaling pathway. In addition, silencing of Alx3 by siRNA inhibited osteoblast differentiation induced by BMP-2, as showed by the expressions of alkaline phosphatase (Alp), Osteocalcin, and Osterix, while over-expression of Alx3 enhanced osteoblast differentiation induced by BMP-2. These results indicate that Alx3 expression is enhanced by BMP-2 via the BMP receptors mediated-Smad signaling and that Alx3 is a positive regulator of osteoblast differentiation induced by BMP-2.
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