AI Article Synopsis
- Dlk2, a protein linked to the regulation of fat cell development, also plays a crucial role in bone health by influencing the formation of osteoclasts, which are cells that break down bone.
- Deleting Dlk2 in osteoclasts leads to fewer of these cells being formed in lab settings and results in stronger bones in live mice.
- The study found that Dlk2 interacts with another protein, Syap1, which affects important signaling pathways (Akt, ERK1/2, and p38) that control osteoclast activity, suggesting that targeting this pathway could help treat bone-related diseases.
Article Abstract
Excessive osteoclast formation and bone resorption are related to osteolytic diseases. Delta drosophila homolog-like 2 (Dlk2), a member of the epidermal growth factor (EGF)-like superfamily, reportedly regulates adipocyte differentiation, but its roles in bone homeostasis are unclear. In this study, we demonstrated that Dlk2 deletion in osteoclasts significantly inhibited osteoclast formation in vitro and contributed to a high-bone-mass phenotype in vivo. Importantly, Dlk2 was shown to interact with synapse-associated protein 1 (Syap1), which regulates Akt phosphorylation at Ser473. Dlk2 deletion inhibited Syap1-mediated activation of the Akt, ERK1/2 and p38 signaling cascades. Additionally, Dlk2 deficiency exhibits increased bone mass in ovariectomized mice. Our results reveal the important roles of the Dlk2-Syap1 signaling pathway in osteoclast differentiation and osteoclast-related bone disorders.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480461 | PMC |
| http://dx.doi.org/10.1038/s41419-023-06107-1 | DOI Listing |
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