A network of trans-cortical capillaries as mainstay for blood circulation in long bones
Anika Grüneboom1,2, Ibrahim Hawwari1, Daniela Weidner2
1Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.
Insights
Trans-cortical vessels (TCVs) are newly discovered capillaries in long bones that connect bone marrow to the periosteal circulation, facilitating immune cell export. These vessels are crucial for vertebrate circulatory systems and immune function.
Area of Science:
- Vascular Biology
- Skeletal Biology
- Immunology
Background:
- Vertebrate organs rely on closed circulatory systems (CCS), but long bone vascularization, particularly for leukocyte egress from bone marrow (BM), remains poorly understood.
- Understanding neutrophil emigration from BM is critical for immune response and bone health.
Purpose of the Study:
- To elucidate the structure and function of the vascular system within murine long bones, focusing on neutrophil emigration from the bone marrow.
- To identify and characterize novel vascular structures involved in bone marrow egress.
Main Methods:
- Microscopic analysis of murine and human long bones to visualize vascular structures.
- Assessment of blood flow and cell transport within identified vessels.
- Genetic and pharmacological manipulation to investigate the role of osteoclasts in TCV formation.
- Induction of inflammatory bone disease to observe TCV adaptation.
Main Results:
- Hundreds of capillaries, termed trans-cortical vessels (TCVs), originate in the BM, traverse the cortical bone perpendicularly, and connect to the periosteal circulation.
- TCVs are present in both murine and human limb bones, express arterial/venous markers, and transport neutrophils.
- Over 80% of arterial and 59% of venous blood flow through TCVs.
- Osteoclast modulation significantly alters TCV numbers, and TCVs proliferate during inflammatory bone conditions.
Conclusions:
- TCVs represent a significant and previously unrecognized component of the CCS in long bones.
- These vessels are a primary route for immune cell export from the bone marrow.
- TCVs play a vital role in bone marrow function and immune surveillance, with potential implications in inflammatory bone diseases.
Abstract:
Closed circulatory systems (CCS) underlie the function of vertebrate organs, but in long bones their structure is unclear, although they constitute the exit route for bone marrow (BM) leukocytes. To understand neutrophil emigration from BM, we studied the vascular system of murine long bones. Here we show that hundreds of capillaries originate in BM, cross murine cortical bone perpendicularly along the shaft and connect to the periosteal circulation. Structures similar to these trans-cortical-vessels (TCVs) also exist in human limb bones. TCVs express arterial or venous markers and transport neutrophils. Furthermore, over 80% arterial and 59% venous blood passes through TCVs. Genetic and drug-mediated modulation of osteoclast count and activity leads to substantial changes in TCV numbers. In a murine model of chronic arthritic bone inflammation, new TCVs develop within weeks. Our data indicate that TCVs are a central component of the CCS in long bones and may represent an important route for immune cell export from the BM.
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