Involvement of Bone Marrow Multipotent Stromal Cells in the Processes Presumably Provoking Vascular Calcification

Area of Science:

• Biomedical Science
• Cell Biology
• Regenerative Medicine

Background:

• The aging process is associated with a decline in the number and function of bone marrow multipotent stromal cells (MSC).
• Bone marrow injury and inflammation can influence the behavior of MSC and osteogenesis.

Purpose of the Study:

• To investigate the effect of aging on bone marrow MSC.
• To examine the impact of bone injury and inflammation on osteogenic MSC.
• To explore the role of BMP-2 in osteogenesis and vascular calcification.

Main Methods:

• Serial transplantation of bone marrow from young and aged mice.
• Medullary curettage in mouse femur to induce bone injury.
• Administration of S. typhimurium antigenic complex (or LPS) and BMP-2.
• Culture of splenic stromal cells with BMP-2.

Main Results:

• Young donor MSC counts surpassed aged donor MSC counts in serial transplantation, indicating age-related decline.
• Bone marrow injury increased total and osteogenic MSC in the contralateral femur and bone marrow transplants.
• Combined administration of LPS and BMP-2 significantly increased osteogenic MSC compared to BMP-2 alone, suggesting inflammation enhances osteogenesis.
• BMP-2 induced osteogenesis in splenic stromal cells, implying a role in vascular calcification.

Conclusions:

• Aging reduces the active pool of bone marrow MSC.
• Bone injury triggers a systemic response that promotes osteogenesis.
• Inflammation, in conjunction with BMP-2, enhances osteogenesis by increasing the pool of inducible MSC.
• Age-related bone changes and osteoporosis may involve similar mechanisms to bone marrow injury, including inflammation and elevated BMP-2, potentially contributing to vascular calcification.