Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, China.
National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, China.
Chin Med J (Engl). 2023 Sep 5;136(17):2077-2085. doi: 10.1097/CM9.0000000000002165.
Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS). Bone marrow stem cells (BMSCs) are a crucial regulator of bone homeostasis. Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia, but the underlying mechanism of this phenomenon remains unclear.
A total of 22 AIS patients and 18 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Bone marrow blood was collected for BMSC isolation and culture. Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group. Furthermore, a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis.
A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed. Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified, including differences in the expression of LRRC17 , DCLK1 , PCDH7 , TSPAN5 , NHSL2 , and CPT1B . Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy. The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group.
Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity, which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.
青少年特发性脊柱侧凸（AIS）患者中已充分证实存在骨质疏松症。骨髓基质干细胞（BMSCs）是骨稳态的关键调节因子。我们之前的研究表明，AIS 相关骨质疏松症患者的 BMSCs 成骨能力降低，但这种现象的潜在机制尚不清楚。
本研究共纳入 22 例 AIS 患者和 18 例年龄匹配的对照者。所有参与者均进行人体测量学和骨量测定。采集骨髓血进行 BMSC 分离和培养。进行成骨和成脂诱导，观察 AIS 相关骨质疏松症组和对照组 BMSCs 分化的差异。此外，从分离的 BMSCs 中提取总 RNA 进行 RNA 测序和后续分析。
AIS 相关骨质疏松症患者的 BMSCs 成骨能力降低，成脂能力增加。AIS 相关骨质疏松症组和对照组之间的 BMSCs 差异表达 mRNAs 被鉴定出来，包括 LRRC17 、DCLK1 、PCDH7 、TSPAN5 、NHSL2 和 CPT1B 等基因的表达差异。京都基因与基因组百科全书（KEGG）富集分析显示，几个参与自噬和线粒体自噬调节的生物学过程。BMSCs 自噬标志物的 Western blot 结果表明，AIS 相关骨质疏松症组的 BMSCs 自噬活性受损。
本研究表明，AIS 相关骨质疏松症患者的 BMSCs 自噬活性降低，这可能与 BMSCs 成骨能力降低、成脂能力升高，进而导致 AIS 患者骨量减少有关。
