The association between parathyroid hormone 1‑34 and the Wnt/β‑catenin signaling pathway in a rat model of osteoarthritis

Ma,Long; Wu,Jiang; Jin,Qun Hua

doi:10.3892/mmr.2017.7762

The association between parathyroid hormone 1‑34 and the Wnt/β‑catenin signaling pathway in a rat model of osteoarthritis

Authors:
- Long Ma
- Jiang Wu
- Qun Hua Jin
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Affiliations: Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: October 11, 2017 https://doi.org/10.3892/mmr.2017.7762
Pages: 8799-8807
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the current study was to determine the effect of parathyroid hormone (PTH) 1‑34 on cartilage degeneration, and the association between PTH 1‑34 and factors associated with the Wnt/β‑catenin pathway following anterior cruciate ligament and medial meniscectomy‑induced osteoarthritis (OA) in rats. A total of 64 Sprague‑Dawley rats were randomly divided into the following four groups: Sham‑operated rats with normal saline (NS)‑treatment (n=16); anterior cruciate ligament transection with partial medial meniscectomy (ACLT + MMx) rats with NS‑treatment (n=16); sham‑operated rats treated with PTH 1‑34 (n=16); and ACLT + MMx rats treated with PTH 1‑34 (n=16). PTH (15 µg/kg/day) was administered via subcutaneous injection 5 days per week from the first postoperative day for 2 or 6 weeks. Staining with hematoxylin and eosin and safranin O, and a scoring system modified by Mankin were used to assess the histopathological features of cartilage. The present study detected the expression of PTH 1 receptor (PTH1R), sclerostin, dickkopf Wnt signaling pathway inhibitor 1 (DKK1), β‑catenin and runt‑related transcription factor 2 (RUNX2) in cartilage by immunohistochemical analysis to determine the association between PTH 1‑34 and factors associated with the Wnt/β‑catenin pathway. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the mRNA expression levels of PTH1R and β‑catenin in cartilage. Histological analysis demonstrated that cartilage degeneration was present post‑surgery and gradually increased over time. PTH 1‑34 reduced the Mankin scores in ACLT + MMx rats compared with the NS‑treated ACLT + MMx rats. Immunohistochemistry and RT‑qPCR analysis demonstrated that, in cartilage, PTH 1‑34 treatment increased the mRNA expression and protein levels of PTH1R and β‑catenin, and decreased protein levels of sclerostin, DKK1 and RUNX2 in ACLT + MMx rats compared with the NS‑treated ACLT + MMx group. The present study demonstrated that PTH 1‑34 upregulated the Wnt/β‑catenin signaling pathway and that PTH1‑34 downregulated RUNX2 through an alternative pathway to the Wnt/β‑catenin signaling pathway, in a rat model of OA.

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