Journal
CELLS
Volume 11, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/cells11203277
Keywords
Dlx genes; skeleton; bone; osteoblasts; chondrocytes; osteoclasts; differentiation; homeobox genes
Categories
Funding
- ANR grant TARGETBONE [ANR-17-CE14-0024]
- Fondation-NRJ-Institut de France [216612]
- Emergence Sorbonne Universite grant DEDUCE
- ATM Cognitio
- ANR grant METABRAIN [ANR-21-CE14-0072]
- ATM DlxUp
- Agence Nationale de la Recherche (ANR) [ANR-17-CE14-0024] Funding Source: Agence Nationale de la Recherche (ANR)
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Skeletal shape and mechanical properties play a crucial role in vertebrate morphology and physical capacities. The development of skeletal morphology depends on communication between chondrocytes, osteoblasts, osteoclasts, and other cellular components of the skeleton. Likewise, skeletal integrity in later stages of life relies on regulatory cascades ensuring the balance between bone formation and resorption.
Skeletal shape and mechanical properties define, to a large extent, vertebrate morphology and physical capacities. During development, skeletal morphogenesis results from dynamic communications between chondrocytes, osteoblasts, osteoclasts, and other cellular components of the skeleton. Later in life, skeletal integrity depends on the regulatory cascades that assure the equilibrium between bone formation and resorption. Finally, during aging, skeletal catabolism prevails over anabolism resulting in progressive skeletal degradation. These cellular processes depend on the transcriptional cascades that control cell division and differentiation in each cell type. Most Distal-less (Dlx) homeobox transcription factors are directly involved in determining the proliferation and differentiation of chondrocytes and osteoblasts and, indirectly, of osteoclasts. While the involvement of Dlx genes in the regulation of skeletal formation has been well-analyzed thanks to several mutant mouse models, the role of these genes in the maintenance of bone integrity has been only partially studied. The importance of Dlx genes for adult bone tissues is evidenced by their central role in the regulatory pathways involving Osx/Sp7 and Runx2, the two major master genes of osteogenesis. Dlx genes appear to be involved in several bone pathologies including, for example, osteoporosis. Indeed, at least five large-scale GWAS studies which aimed to detect loci associated with human bone mineral density (BMD) have identified a known DLX5/6 regulatory region within chromosome 7q21.3 in proximity of SEM1/FLJ42280/DSS1 coding sequences, suggesting that DLX5/6 expression is critical in determining healthy BMD. This review aims to summarize the major findings concerning the involvement of Dlx genes in skeletal development and homeostasis and their involvement in skeletal aging and pathology.
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