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Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes

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Published on: January 27, 2023

The Lymphatic Endothelial Cell Secretome Inhibits Osteoblast Differentiation and Bone Formation.

Ernesto Solorzano^1,2,3, Andrew L Alejo¹, Hope C Ball^1,2,3

¹Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA.

|October 27, 2023

Summary

Complex lymphatic anomalies (CLAs) cause bone loss by affecting bone-forming cells. Researchers found that substances from lymphatic endothelial cells (L-CM) suppress osteoblasts, hindering bone formation in CLAs.

Keywords:

Gorham–Stout disease bone bone formation complex lymphatic anomaly conditioned medium lymphatic endothelial cell osteoblast osteopathy

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Area of Science:

Rare diseases
Vascular anomalies
Skeletal biology

Background:

Complex lymphatic anomalies (CLAs) are rare diseases characterized by abnormal lymphatic vessels that invade bone.
Bone resorption, driven by overactive osteoclasts, is observed in CLAs, but the mechanism of progressive bone loss is unclear.
The role of osteoblasts, the cells responsible for bone formation, in CLAs has not been fully investigated.

Purpose of the Study:

To investigate the impact of lymphatic endothelial cell secretome on osteoblast differentiation and function.
To determine if lymphatic endothelial cell conditioned medium (L-CM) affects bone formation processes.

Main Methods:

Osteoblasts were cultured and treated with L-CM.
Osteoblast proliferation, differentiation, and function were assessed.
Neonatal calvaria explant cultures were used to evaluate L-CM's effect on bone formation.

Main Results:

L-CM significantly reduced osteoblast proliferation, differentiation, and function.
L-CM treatment inhibited bone formation in neonatal calvaria explant cultures.
These results suggest osteoblast suppression is a key mechanism in CLA-associated bone loss.

Conclusions:

Osteoblasts are actively suppressed by factors released from lymphatic endothelial cells in CLAs.
This suppression of osteoblasts contributes to the progressive bone loss observed in CLA patients.
These findings reveal a novel mechanism underlying the unique osteopathic profiles in complex lymphatic anomalies.