Department of Orthopaedic Surgery, Tianjin Medical University General Hospital, Tianjin, China (mainland).
Med Sci Monit. 2019 Jan 8;25:259-268. doi: 10.12659/MSM.913752.
BACKGROUND Intermittent parathyroid hormone (PTH) 1-34 administration stimulates osteogenesis and increases bone marrow mesenchymal stem cell (MSC) density; however, its effect on the circulating MSCs is unknown. This study aimed to examine the effect of intermittent PTH 1-34 administration on circulating MSCs in the peripheral blood of postmenopausal osteoporotic women. MATERIAL AND METHODS Fifty-four postmenopausal osteoporotic women at high risk of fracture were enrolled and administered either teriparatide (PTH 1-34) or alendronate for 12 months. Whole blood samples were obtained at baseline, 1, 3, 6, and 12 months after initiation of treatment. Flow cytometry analyses were performed to identify circulating MSCs (CD73+, CD90+, CD105+, CD34-, and CD45-). Serum markers of bone formation, bone resorption, as well as bone mineral density (BMD) were serially measured. Circulating MSCs were isolated from peripheral blood of teriparatide treated women and cultured in osteogenic medium to examine their osteogenic differentiation potential. RESULTS Teriparatide treatment increased circulating MSCs to 141±96% (P<0.001) by month 1, persisting until month 12; this increase was positively associated with increases in bone formation and bone resorption biomarkers (at month 6) and spine BMD (at month 12). Furthermore, intermittent PTH 1-34 administration promoted in vitro osteogenic differentiation of circulating MSCs, evident from increased alkaline phosphatase (ALP) activity, ALP-expressing cell density, calcium deposition, and Runx-2, OSX, COL 1a1, and osteocalcin mRNA upregulation. CONCLUSIONS Intermittent PTH 1-34 administration increased circulating MSC density in women with postmenopausal osteoporosis and enhanced in vitro osteogenic differentiation potential of these cells.
间歇性甲状旁腺激素（PTH）1-34 给药可刺激成骨作用并增加骨髓间充质干细胞（MSC）密度；然而，其对循环 MSC 的影响尚不清楚。本研究旨在研究间歇性 PTH 1-34 给药对绝经后骨质疏松症女性外周血循环 MSC 的影响。
纳入 54 例有骨折高风险的绝经后骨质疏松症女性，分别给予特立帕肽（PTH 1-34）或阿仑膦酸钠治疗 12 个月。在开始治疗后的基线、1、3、6 和 12 个月时采集全血样本。采用流式细胞术分析鉴定循环 MSC（CD73+、CD90+、CD105+、CD34-和 CD45-）。连续测量血清骨形成标志物、骨吸收标志物以及骨密度（BMD）。从特立帕肽治疗女性的外周血中分离循环 MSC 并在成骨培养基中培养，以检测其成骨分化潜能。
特立帕肽治疗 1 个月时使循环 MSC 增加至 141±96%（P<0.001），并持续至 12 个月；这种增加与骨形成和骨吸收标志物（6 个月时）和脊柱 BMD（12 个月时）的增加呈正相关。此外，间歇性 PTH 1-34 给药促进了循环 MSC 的体外成骨分化，表现为碱性磷酸酶（ALP）活性、ALP 表达细胞密度、钙沉积以及 Runx-2、OSX、COL 1a1 和骨钙素 mRNA 的上调。
间歇性 PTH 1-34 给药增加了绝经后骨质疏松症女性的循环 MSC 密度，并增强了这些细胞的体外成骨分化潜能。
