Abstract

BackgroundAlthough 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.MethodsCPCs 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.ResultsMigratory 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.ConclusionsOur 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.

Highlights

  • Knee osteoarthritis (KOA) is one of the most common degenerative disorders in joints and has been anticipated to be the fourth leading cause of disability worldwide by the year 2020 [1, 2]

  • The morphological characteristics of Migratory CPCs (mCPCs) of knee OA patients The cartilaginous tissues for chondrogenic progenitor cells (CPCs) culturing were harvested from the articular cartilages of knee OA patients (Fig. 1a, b)

  • The results showed that the expressions of genes encoding chemokines proteins (CXCL6 and CXCL1) significantly upregulated, but the expressions of genes encoding growth factor and extracellular matrix (ECM) proteins (HGF and LAMA5) were remarkably decreased (Fig. 5d)

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Summary

Introduction

Knee osteoarthritis (KOA) is one of the most common degenerative disorders in joints and has been anticipated to be the fourth leading cause of disability worldwide by the year 2020 [1, 2]. It is mainly characterized by slowly progressive degeneration and loss of the articular cartilage. Recent investigations have shown the normal and OA articular cartilages containing tissue-specific stem/progenitor cells, named chondrogenic progenitor cells (CPCs), with high proliferative, clonogenic, and multi-differentiation capacities [5, 6]. 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

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