Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice

Pinch1 and Pinch2 are LIM domain-containing proteins with crucial functions in mediating focal adhesion formation. Our previous studies have demonstrated that Pinch1/2 expression is essential for cartilage and bone formation during skeletal development in mice. Loss of Pinch expression (Prx1Cre; Pin...

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Main Authors: Xiaohao Wu, Sixiong Lin, Rongdong Liao, Qing Yao, Lijun Lin, Xuenong Zou, Guozhi Xiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1116128/full
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author Xiaohao Wu
Sixiong Lin
Rongdong Liao
Qing Yao
Lijun Lin
Xuenong Zou
Guozhi Xiao
author_facet Xiaohao Wu
Sixiong Lin
Rongdong Liao
Qing Yao
Lijun Lin
Xuenong Zou
Guozhi Xiao
author_sort Xiaohao Wu
collection DOAJ
description Pinch1 and Pinch2 are LIM domain-containing proteins with crucial functions in mediating focal adhesion formation. Our previous studies have demonstrated that Pinch1/2 expression is essential for cartilage and bone formation during skeletal development in mice. Loss of Pinch expression (Prx1Cre; Pinch1flox/flox; Pinch2−/−) inhibits chondrocyte proliferation and promotes chondrocyte apoptosis, resulting in severe chondrodysplasia and limb shortening. Based on these observations, we wonder if Pinch proteins have a role in adult cartilage and whether Pinch deficiency will compromise cartilage homeostasis and promote osteoarthritis (OA)-related defects in adult mice. To this end, we generated the AggrecanCreERT2; Pinch1flox/flox; Pinch2−/− mice, in which the Pinch1 gene can be inducibly deleted in aggrecan-expressing chondrocytes by tamoxifen and the Pinch2 gene is globally inactivated. Immunofluorescent staining confirmed that the expression of Pinch proteins was significantly decreased in articular cartilage in tamoxifen-treated adult AggrecanCreERT2; Pinch1flox/flox; Pinch2−/− mice. Unexpectedly, our results showed that Pinch loss did not induce marked abnormalities in articular cartilage and other joint tissues in the knee joints of either adult (10-month-old) mice or aged (17-month-old) mice. In a destabilization of the medial meniscus (DMM)-induced OA model, the surgically-induced OA lesions were comparable between Pinch-deficient mice and control mice. Given the fact that Pinch proteins are essential for chondrogenesis and cartilage formation during skeletal development, these findings suggest that Pinch expression is seemingly not indispensable for adult cartilage homeostasis in mice.
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spelling doaj.art-d3a929213ac04e26a51e46cc73128dda2023-01-19T05:31:17ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-01-011110.3389/fcell.2023.11161281116128Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult miceXiaohao Wu0Sixiong Lin1Rongdong Liao2Qing Yao3Lijun Lin4Xuenong Zou5Guozhi Xiao6Department of Biochemistry, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaDepartment of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Biochemistry, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaPinch1 and Pinch2 are LIM domain-containing proteins with crucial functions in mediating focal adhesion formation. Our previous studies have demonstrated that Pinch1/2 expression is essential for cartilage and bone formation during skeletal development in mice. Loss of Pinch expression (Prx1Cre; Pinch1flox/flox; Pinch2−/−) inhibits chondrocyte proliferation and promotes chondrocyte apoptosis, resulting in severe chondrodysplasia and limb shortening. Based on these observations, we wonder if Pinch proteins have a role in adult cartilage and whether Pinch deficiency will compromise cartilage homeostasis and promote osteoarthritis (OA)-related defects in adult mice. To this end, we generated the AggrecanCreERT2; Pinch1flox/flox; Pinch2−/− mice, in which the Pinch1 gene can be inducibly deleted in aggrecan-expressing chondrocytes by tamoxifen and the Pinch2 gene is globally inactivated. Immunofluorescent staining confirmed that the expression of Pinch proteins was significantly decreased in articular cartilage in tamoxifen-treated adult AggrecanCreERT2; Pinch1flox/flox; Pinch2−/− mice. Unexpectedly, our results showed that Pinch loss did not induce marked abnormalities in articular cartilage and other joint tissues in the knee joints of either adult (10-month-old) mice or aged (17-month-old) mice. In a destabilization of the medial meniscus (DMM)-induced OA model, the surgically-induced OA lesions were comparable between Pinch-deficient mice and control mice. Given the fact that Pinch proteins are essential for chondrogenesis and cartilage formation during skeletal development, these findings suggest that Pinch expression is seemingly not indispensable for adult cartilage homeostasis in mice.https://www.frontiersin.org/articles/10.3389/fcell.2023.1116128/fullPinchfocal adhesionarticular cartilageosteoarthritishomeostasis
spellingShingle Xiaohao Wu
Sixiong Lin
Rongdong Liao
Qing Yao
Lijun Lin
Xuenong Zou
Guozhi Xiao
Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice
Frontiers in Cell and Developmental Biology
Pinch
focal adhesion
articular cartilage
osteoarthritis
homeostasis
title Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice
title_full Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice
title_fullStr Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice
title_full_unstemmed Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice
title_short Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice
title_sort brief research report effects of pinch deficiency on cartilage homeostasis in adult mice
topic Pinch
focal adhesion
articular cartilage
osteoarthritis
homeostasis
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1116128/full
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