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Published on: December 18, 2019
Lack of ADAM10 in endothelial cells affects osteoclasts at the chondro-osseus junction
Ren Zhao1, Aimin Wang, Katherine C Hall
1Department of Orthopedics, Daping Hospital, Third Military Medical University, Chongqing, 400042, P.R. China; Arthritis and Tissue Degeneration Program, New York, New York, 10021.
Insights
Endothelial cells regulate bone growth by controlling osteoclast formation. Mice lacking ADAM10 in endothelial cells show reduced osteoclasts and shorter long bones, indicating a crucial role for ADAM10 in bone development.
Area of Science:
- Vascular biology
- Skeletal biology
- Cell biology
Background:
- Endothelial cells play a role in regulating bone development.
- The specific mechanisms by which endothelial cells influence long bone growth are not fully understood.
- ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) is involved in cell-cell interactions and signaling.
Purpose of the Study:
- To investigate the role of ADAM10 in endothelial cells in regulating long bone growth.
- To determine how endothelial cell-specific deletion of ADAM10 affects bone development and cellular composition of growth plates.
- To explore the potential link between endothelial cells, osteoclastogenesis, and bone length.
Main Methods:
- Histopathological evaluation of femur and tibia growth plates in Adam10ΔEC mice and controls at various postnatal stages.
- Assessment of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts at the chondro-osseous junction (COJ).
- Analysis of endothelial cell distribution using endomucin staining in the growth plate vasculature.
Main Results:
- Adam10ΔEC mice exhibited shorter long bones (femur, tibia, humerus) compared to controls.
- Growth plates showed a thickened zone of hypertrophic chondrocytes and increased trabecular bone density by P21.
- A significant reduction in TRAP-positive osteoclasts at the COJ was observed in Adam10ΔEC mice from P21 onwards.
- Increased density of endomucin-stained endothelial cells was noted at the COJ starting from P7.
Conclusions:
- Endothelial cell-specific deletion of ADAM10 leads to impaired long bone growth, potentially due to reduced osteoclastogenesis.
- ADAM10 in endothelial cells is critical for regulating endothelial cell organization within the bone vasculature.
- This study provides in vivo evidence for endothelial cell regulation of osteoclast function, highlighting a novel mechanism in bone development.
Abstract:
Mice lacking ADAM10 in endothelial cells (Adam10ΔEC mice) have shorter femurs, tibiae, and humeri than controls, raising questions about how endothelial cells could control long bone growth. We performed a histopathological evaluation of the femur and tibia growth plates at different postnatal stages, and assessed the distribution of TRAP-positive osteoclasts and endothelial cells at the growth plate. The growth plates in Adam10ΔEC mice appeared normal at P7 and P14, but a thickened zone of hypertrophic chondrocytes and increased trabecular bone density were apparent by P21 and later. The number of TRAP+ cells at the COJ was normal at P7 and P14, but was strongly reduced at P21 and later. Moreover, the density of endomucin-stained endothelial cells at the COJ was increased starting at P7. The defects in long bone growth in Adam10ΔEC mice could be caused by a lack of osteoclastogenesis at the COJ. Moreover, ADAM10 appears to regulate endothelial cell organization in the developing bone vasculature, perhaps in a similar manner as in the developing retinal vascular tree, where ADAM10 is thought to control Notch-dependent endothelial cell fate decisions. This study provides evidence for the regulation of osteoclast function by endothelial cells in vivo.
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