Department of Orthopedics, the First Medical Center, Chinese PLA General Hospital, Beijing, P.R. China.
Contributed equally as first authors.
Cell Transplant. 2021 Jan-Dec;30:9636897211053870. doi: 10.1177/09636897211053870.
Osteonecrosis of the femoral head (ONFH) is a leading cause of mobility impairment which may lead to a total hip replacement. Recent studies have found tendon derived stem cells (TDSCs) might be an ideal cell source for musculoskeletal tissue regeneration. And our previous study has shown Sox11 could promote osteogenesis of bone marrow-derived MSCs. However, the effect of TDSCs or Sox11 over-expressing TDSCs (TDSCs-Sox11) on bone regeneration in ONFH has not been investigated. In the present study, TDSCs were infected with AAV carrying Sox11 or empty vector. We showed that Sox11 could promote the proliferation and osteogenic differentiation of TDSCs, as well as angiogenesis in vitro. The western blot analysis showed that Sox11 could activate the PI3K/Akt signaling pathway to promote osteogenesis of TDSCs. Finally, using a rabbit model of hormone-induced ONFH, our result demonstrated that local administration of TDSCs or TDSCs overexpressing Sox11 could accelerate bone regeneration in necrotic femoral heads, and TDSCs overexpressing Sox11 showed better effects. TDSCs over-expressing Sox11 might be a promising cell source for stem cell therapy to promote bone regeneration, such as ONFH, fracture, bone defect, and so on.
股骨头坏死（ONFH）是导致活动能力丧失的主要原因，可能需要进行全髋关节置换。最近的研究发现，肌腱衍生干细胞（TDSCs）可能是肌肉骨骼组织再生的理想细胞来源。我们之前的研究表明 Sox11 可以促进骨髓间充质干细胞的成骨作用。然而，TDSCs 或 Sox11 过表达 TDSCs（TDSCs-Sox11）对 ONFH 中骨再生的影响尚未得到研究。在本研究中，用携带 Sox11 或空载体的 AAV 感染 TDSCs。我们表明 Sox11 可以促进 TDSCs 的增殖和成骨分化，以及体外血管生成。Western blot 分析表明 Sox11 可以激活 PI3K/Akt 信号通路，促进 TDSCs 的成骨作用。最后，使用激素诱导的兔 ONFH 模型，我们的结果表明，局部给予 TDSCs 或 Sox11 过表达 TDSCs 可以加速坏死股骨头的骨再生，而过表达 Sox11 的 TDSCs 效果更好。过表达 Sox11 的 TDSCs 可能是一种有前途的细胞来源，可用于干细胞治疗以促进骨再生，如 ONFH、骨折、骨缺损等。
