From the Department of Osteoporosis and Bone Disease, Huadong Hospital, affiliated to Fudan University, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute; the Department of Orthopedics, Huadong Hospital, affiliated to Fudan University; and the Central Laboratory, Huadong Hospital, affiliated to Fudan University, Shanghai, China.
Q. Cheng, MD, PhD, Department of Osteoporosis and Bone Disease, Huadong Hospital, affiliated to Fudan University, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute; S. Lin, MD, Department of Orthopedics, Huadong Hospital, affiliated to Fudan University; B. Bi, MD, PhD, Central Lab, Huadong Hospital, affiliated to Fudan University; X. Jiang, MD, Department of Osteoporosis and Bone Disease, Huadong Hospital affiliated to Fudan University, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute; H. Shi, MD, Department of Osteoporosis and Bone Disease, Huadong Hospital, affiliated to Fudan University, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute; Y. Fan, MD, PhD, Department of Orthopedics, Huadong Hospital, affiliated to Fudan University; W. Lin, MD, Department of Orthopedics, Huadong Hospital, affiliated to Fudan University; Y. Zhu, MD, Department of Orthopedics, Huadong Hospital, affiliated to Fudan University; F. Yang, MD, PhD, Department of Orthopedics, Huadong Hospital, affiliated to Fudan University. Qun Cheng and Shangjin Lin are co-first authors of this article.
J Rheumatol. 2018 Dec;45(12):1696-1704. doi: 10.3899/jrheum.171226. Epub 2018 Sep 1.
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 (), angiopoietin 2 (), and the osteoblast-specific genes runt-related transcription factor 2 ( and 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, , and , 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.
人们认为骨骼中的血管会影响骨骼的成骨作用。目前尚无临床研究确定血管生成是否与骨量和生长因子的基因表达有关。我们比较了发生脆性骨折的绝经后妇女、骨质疏松症或伴有正常骨量的外伤性骨折的骨髓内皮祖细胞（EPC），以控制骨骼的血管生成。
从年龄匹配的骨质疏松症或 COM 患者中获取骨标本。分离单核细胞，通过流式细胞术检测 EPC。测量特定基因的表达水平。测定骨矿物质密度（BMD），并测定骨转换的血清标志物。使用学生 t 检验或曼-惠特尼 U 检验评估 OP 和 COM 之间的差异，并用 Spearman 相关系数确定相关性。
与 COM 相比，OP 患者的血清骨钙素、I 型前胶原 N 端前肽和 25-羟维生素 D 水平明显降低，总髋部和股骨颈 BMD 降低，骨髓 EPC 减少。OP 患者的血管内皮生长因子、血管生成素 1（）、血管生成素 2（）和骨特异性基因 runt 相关转录因子 2（）和（）在骨骼中的表达水平明显低于 COM。我们确定成熟 EPC 与股骨颈和总髋部的 BMD、Ang-1、、和的基因表达呈正相关，与核因子-κB 配体受体激活剂和 Ang-2 的基因表达呈负相关。
我们的结果表明骨髓 EPC 与骨量和生长因子的基因表达相关，这支持了血管生成和骨骼生成之间存在相互作用的假说。
