Effect of parathyroid hormone on early chondrogenic differentiation from mesenchymal stem cells.

Yun Zhang,Tomoyuki Saito,Ken Kumagai

doi:10.1186/s13018-014-0068-5

Yun Zhang, Tomoyuki Saito + Show 1 more

Open Access

https://doi.org/10.1186/s13018-014-0068-5

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Abstract

BackgroundTreatment of articular cartilage injuries remains a difficult challenge due to the limited capacity for intrinsic repair. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes under certain culture conditions. This study focused on the modulatory effects of parathyroid hormone (PTH) on chondrogenic differentiation from MSCs.MethodsMSCs were treated with various concentrations of PTH under chondrogenic pellet culture condition. RNA was isolated for real-time polymerase chain reaction (PCR) and gene expressions of collagen type II α1 chain (Col2a1), collagen type X α1 chain, collagen type I α1 chain, SRY-box9 (Sox9), and type 1 PTH/PTHrP receptor (PTH1R) were examined. Chondrogenic differentiation was also evaluated by histological findings.ResultsPTH had opposite effects on chondrogenesis, depending on the concentration. A low to moderate concentration of PTH promoted chondrogenic differentiation of MSCs with increased expression of Sox9, Col2a1, and PTH1R, whereas chondrogenesis of MSCs was inhibited rather than stimulated with a higher concentration of PTH.ConclusionThis study provides insights into the modulatory effect of PTH on chondrogenic differentiation from MSCs and the therapeutic potential for cartilage regeneration. Based on clinical experience regarding the efficacy and safety of PTH for bone metabolism, PTH may also be useful clinically for cartilage repair.

Highlights

Treatment of articular cartilage injuries remains a difficult challenge due to the limited capacity for intrinsic repair
Sections from cells treated with 10 nM parathyroid hormone (PTH) exhibited more chondrocyte-like cells with large round nuclei than cells treated with 100 nM PTH
To further address chondrogenic differentiation, we examined the deposition of type II collagen, which is a major component of the cartilage extracellular matrix (Figure 1F,G,H,I,J)

Summary

Introduction

Treatment of articular cartilage injuries remains a difficult challenge due to the limited capacity for intrinsic repair. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes under certain culture conditions. This study focused on the modulatory effects of parathyroid hormone (PTH) on chondrogenic differentiation from MSCs. Treatment of articular cartilage injuries remains a difficult challenge due to the limited capacity for intrinsic repair. Cell-based approaches are key to successful tissue engineering [2]. Mesenchymal stem cells (MSCs) are the most commonly used cell source with a high self-renewal capacity, multilineage potential, and easy isolation from several human tissues including bone marrow [3,4]. MSCs can differentiate into chondrocytes under certain culture conditions [5,6] and have been used for cartilage regeneration

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