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Published on: September 14, 2021
E-selectin ligand 1 regulates bone remodeling by limiting bioactive TGF-β in the bone microenvironment
Tao Yang1, Ingo Grafe, Yangjin Bae
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Summary
E-selectin ligand-1 (ESL-1) deficiency causes osteopenia by increasing bone resorption and decreasing mineralization. ESL-1 regulates transforming growth factor-beta (TGF-β) maturation in osteoblasts, crucial for bone homeostasis and coupled remodeling.
Area of Science:
- Skeletal Biology
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor-beta (TGF-β) is vital for skeletal homeostasis.
- E-selectin ligand-1 (ESL-1) regulates TGF-β bioavailability in cartilage.
- The role of ESL-1 in bone homeostasis and TGF-β maturation is undefined.
Purpose of the Study:
- To investigate the role of ESL-1 in bone homeostasis.
- To determine if ESL-1 regulates TGF-β maturation in bone cells.
- To elucidate the mechanism by which ESL-1 influences bone remodeling.
Main Methods:
- Generation and analysis of Esl-1 knockout (Esl-1(-/-)) mice.
- Primary osteoblast and osteoclast progenitor cultures.
- Osteoblast-osteoclast co-culture assays.
- Analysis of TGF-β signaling pathway components and bone remodeling markers.
- In vivo treatment with a TGF-β neutralizing antibody (1D11).
Main Results:
- Esl-1(-/-) mice exhibit severe osteopenia, characterized by increased bone resorption and decreased mineralization.
- ESL-1 deficiency in osteoblasts leads to impaired differentiation and enhanced osteoclastogenesis stimulation.
- Elevated mature TGF-β/pro-TGF-β ratio and increased expression of TGF-β downstream targets and osteoclastogenic factors were observed in Esl-1(-/-) calvaria.
- In vivo blockade of TGF-β signaling ameliorated the osteopenic phenotype in Esl-1(-/-) mice.
Conclusions:
- ESL-1 is a critical regulator of bone homeostasis, primarily acting in osteoblasts.
- ESL-1 modulates intracellular TGF-β maturation, impacting bone remodeling.
- Dysregulation of ESL-1-mediated TGF-β signaling contributes to osteopenia and impaired osteoblast-osteoclast coupling.
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