Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, China; and.
FASEB J. 2019 Aug;33(8):8913-8924. doi: 10.1096/fj.201802711R. Epub 2019 Apr 24.
Osteoporosis is a major health problem, making bones fragile and susceptible to fracture. Previous works showed that mechanical loading stimulated bone formation and accelerated fracture healing. Focusing on the role of Wnt3a (wingless/integrated 3a), this study was aimed to assess effects of mechanical loading to the spine, using ovariectomized (OVX) mice as a model of osteoporosis. Two-week daily application of this novel loading (4 N, 10 Hz, 5 min/d) altered bone remodeling with an increase in Wnt3a. Spinal loading promoted osteoblast differentiation, endothelial progenitor cell migration, and tube formation and inhibited osteoclast formation, migration, and adhesion. A transient silencing of Wnt3a altered the observed loading effects. Spinal loading significantly increased bone mineral density, bone mineral content, and bone area per tissue area. The loaded OVX group showed a significant increase in the number of osteoblasts and reduction in osteoclast surface/bone surface. Though expression of osteoblastic genes was increased, the levels of osteoclastic genes were decreased by loading. Spinal loading elevated a microvascular volume as well as VEGF expression. Collectively, this study supports the notion that Wnt3a-mediated signaling involves in the effect of spinal loading on stimulating bone formation, inhibiting bone resorption, and promoting angiogenesis in OVX mice. It also suggests that Wnt3a might be a potential therapeutic target for osteoporosis treatment.-Li, X., Liu, D., Li, J., Yang, S., Xu, J., Yokota, H., Zhang, P. Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model.
骨质疏松症是一个主要的健康问题，使骨骼脆弱并容易骨折。以前的研究表明，机械负荷刺激骨形成并加速骨折愈合。本研究聚焦于 Wnt3a（无翅型整合 3a）的作用，旨在评估机械负荷对脊柱的影响，使用去卵巢（OVX）小鼠作为骨质疏松症的模型。这种新型负荷（4 N，10 Hz，5 min/d）的每周两次应用改变了骨重塑，增加了 Wnt3a。脊柱负荷促进成骨细胞分化、内皮祖细胞迁移和管状形成，并抑制破骨细胞形成、迁移和黏附。Wnt3a 的瞬时沉默改变了观察到的负荷效应。脊柱负荷显著增加了骨密度、骨矿物质含量和组织面积的骨面积。负荷的 OVX 组的成骨细胞数量显著增加，破骨细胞表面/骨表面减少。虽然成骨基因的表达增加，但负荷降低了破骨基因的水平。脊柱负荷增加了微血管体积和 VEGF 表达。总之，本研究支持这样一种观点，即 Wnt3a 介导的信号转导参与了脊柱负荷对刺激骨形成、抑制骨吸收和促进 OVX 小鼠血管生成的作用。它还表明，Wnt3a 可能是骨质疏松症治疗的潜在治疗靶点。-李，X.，刘，D.，李，J.，杨，S.，徐，J.，横田，H.，张，P. Wnt3a 参与机械负荷改善绝经后骨质疏松症小鼠模型的骨重塑和血管生成。
