Bone Marrow-derived Endothelial Progenitor Cells Are Associated with Bone Mass and Strength.

Abstract

Blood vessels of bone are thought to influence osteogenesis of bone. No clinical studies have determined whether angiogenesis is related to bone mass and gene expression of growth factors. We compared bone marrow endothelial progenitor cells (EPC), which control angiogenesis of bone in postmenopausal women incurring fragility fracture, with osteoporosis or traumatic fracture with normal bone mass (COM). Bone specimens were obtained from age-matched women with osteoporosis or COM. Mononuclear cells were isolated and EPC were detected by flow cytometry. The expression levels of specific genes were measured. Bone mineral density (BMD) was determined, and serum markers of bone turnover also were measured. Differences between OP and COM were assessed with Student t test or Mann-Whitney U test, and correlations were determined using Spearman's correlation. Compared with COM, patients with OP had significantly lower levels of serum osteocalcin, procollagen type-1 N-terminal propeptide, and 25-hydroxy vitamin D, as well as decreased BMD of total hip and femoral neck and fewer bone marrow EPC. Expression levels of vascular endothelial growth factor, angiopoietin-1 (<i>Ang-1</i>), angiopoietin 2 (<i>Ang-2</i>), and the osteoblast-specific genes runt-related transcription factor 2 (<i>RUNX2)</i> and <i>osterix</i> in bone were significantly lower in OP than in COM. We determined that mature EPC were correlated positively with BMD of the femoral neck and total hip, gene expression of Ang-1, <i>RUNX2</i>, and <i>CD31</i>, and negatively with gene expression of receptor activator of nuclear factor-κB ligand and Ang-2. Our results demonstrate correlations of bone marrow EPC with bone mass and gene expression of growth factors, which support a hypothesis of crosstalk between angiogenesis and osteogenesis in bone health.