The osteoarthritis‑associated gene PAPSS2 promotes differentiation and matrix formation in ATDC5 chondrogenic cells

Fan,Liying; He,Yuan; Han,Jing; Yuan,Puwei; Guo,Xiong; Wang,Weizhuo

doi:10.3892/etm.2018.6843

The osteoarthritis‑associated gene PAPSS2 promotes differentiation and matrix formation in ATDC5 chondrogenic cells

Authors:
- Liying Fan
- Yuan He
- Jing Han
- Puwei Yuan
- Xiong Guo
- Weizhuo Wang
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Affiliations: Department of Orthopedic Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Beijing Novartis Pharma Ltd., Beijing 100004, P.R. China, Department of Public Health, Key Laboratory of Environment and Genes Related to Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Orthopedics, The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712000, P.R. China
Published online on: October 11, 2018 https://doi.org/10.3892/etm.2018.6843
Pages: 5190-5200
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

3'‑Phosphoadenosine 5'‑phosphosulfate synthetase 2 (PAPSS2) has been shown to be important in the development of normal skeletal structure. The aim of the present study was to evaluate the role of PAPSS2 in the differentiation of chondrocytes as well as their mechanisms. Using RNA interference‑mediated via a lentivirus and a retrovirus, PAPSS2 gene silence and overexpression in ATDC5 chondrogenic cells were performed. Chondrocyte differentiation and chondrogenic‑related gene markers associated with extracellular matrix formation were noted. The mRNA and protein expression for Wnt4, β‑catenin and SOX9 genes were observed. The PAPSS2 transcript expression levels progressively decline in ATDC5‑induced chondrocyte‑like cells during differentiation. Silencing of PAPSS2 expression had a significantly attenuating effect on cell differentiation and decreased expression of collagen II and X. In contrast, over‑expression of PAPSS2 promoted the differentiation of ATDC5 chondrogenic cells. The mRNA expression levels of Wnt4 and SOX9 decreased significantly in PAPSS2 knock down cells vs. control cells. However, this expression was increased in the cells over‑expressing PAPSS2. These data indicate that PAPSS2 regulates aggrecan activity as well as cell differentiation. The findings favor a mechanism by which PAPSS2 induces differentiation in ATDC5 cells via direct regulation of early signaling events that promote formation of collagenous matrix components. This control is probably mediated via extracellular matrix formation Wnt/β‑catenin signaling pathways.

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