BACKGROUND Although increasing studies have demonstrated that chondrogenic progenitor cells (CPCs) remain present in human osteoarthritic cartilage, the biological alterations of the CPCs from the less diseased lateral tibial condyle and the more diseased medial condyle of same patient remain to be investigated. METHODS CPCs were isolated from paired grade 1-2 and grade 3-4 osteoarthritic cartilage by virtue of cell migratory capacities. The cell morphology, immunophenotype, self-renewal, multi-differentiation, and cell migration of these CPCs were evaluated. Additionally, the distributions of CD105+/CD271+ cells in OA osteochondral specimen were determined. Furthermore, a high-throughput mRNA sequencing was performed. RESULTS Migratory CPCs (mCPCs) robustly outgrew from mildly collagenases-digested osteoarthritic cartilages. The mCPCs from grade 3-4 cartilages (mCPCs, grades 3-4) harbored morphological characteristics, cell proliferation, and colony formation capacity that were similar to those of the mCPCs from the grade 1-2 OA cartilages (mCPCs, grades 1-2). However, the mCPCs (grades 3-4) highly expressed CD271. In addition, the mCPCs (grades 3-4) showed enhanced osteo-adipogenic activities and decreased chondrogenic capacity. Furthermore, the mCPCs (grades 3-4) exhibited stronger cell migration in response to osteoarthritis synovial fluids. More CD105+/CD271+ cells resided in grade 3-4 articular cartilages. Moreover, the results of mRNA sequencing showed that mCPCs (grades 3-4) expressed higher migratory molecules. CONCLUSIONS Our data suggest that more mCPCs (grades 3-4) migrate to injured articular cartilages but with enhanced osteo-adipogenic and decreased chondrogenic capacity, which might explain the pathological changes of mCPCs during the progression of OA from early to late stages. Thus, these dysfunctional mCPCs might be optional cell targets for OA therapies.

中文翻译：

---

膝骨关节炎进展过程中迁徙软骨祖细胞的生物潜力改变。

背景技术尽管越来越多的研究表明，软骨形成祖细胞（CPC）仍然存在于人的骨关节炎软骨中，但同一患者的患病少的胫骨外侧con和患病的内侧con的CPC的生物学改变仍有待研究。方法利用细胞迁移能力从成对的1-2级和3-4级骨关节炎软骨中分离CPC。评估了这些CPC的细胞形态，免疫表型，自我更新，多分化和细胞迁移。另外，测定了OA骨软骨样品中CD105 + / CD271 +细胞的分布。此外，进行了高通量mRNA测序。结果迁移的CPCs（mCPC）明显超过了轻度胶原酶消化的骨关节炎软骨的生长。来自3-4级软骨（mCPC，3-4级）的mCPC具有与来自1-2级OA软骨（mCPC，1-2级）的mCPC相似的形态特征，细胞增殖和集落形成能力）。但是，mCPC（3-4级）高度表达CD271。此外，mCPC（3-4级）显示出增强的骨成脂活性和降低的软骨形成能力。此外，mCPC（3-4级）对骨关节炎滑膜液表现出更强的细胞迁移。更多的CD105 + / CD271 +细胞驻留在3-4级关节软骨中。此外，mRNA测序的结果表明，mCPC（3-4级）表达了更高的迁移分子。结论我们的数据表明，更多的mCPC（3-4级）迁移至受伤的关节软骨，但骨成脂能力增强，软骨形成能力降低，这可能解释了OA从早期到晚期发展过程中mCPC的病理变化。因此，这些功能异常的mCPC可能是OA治疗的可选细胞靶标。