Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway

Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the...

Full description

Bibliographic Details
Main Authors: Xin Zhang, Shibin Shu, Zhenhua Feng, Yong Qiu, Hongda Bao, Zezhang Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1102318/full
_version_ 1797942905553289216
author Xin Zhang
Shibin Shu
Zhenhua Feng
Yong Qiu
Hongda Bao
Zezhang Zhu
author_facet Xin Zhang
Shibin Shu
Zhenhua Feng
Yong Qiu
Hongda Bao
Zezhang Zhu
author_sort Xin Zhang
collection DOAJ
description Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD.
first_indexed 2024-04-10T20:14:56Z
format Article
id doaj.art-ce53c2db8a274cd6952d89a7f8c158e5
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-04-10T20:14:56Z
publishDate 2023-01-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-ce53c2db8a274cd6952d89a7f8c158e52023-01-26T05:59:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-01-011410.3389/fphar.2023.11023181102318Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathwayXin ZhangShibin ShuZhenhua FengYong QiuHongda BaoZezhang ZhuIntervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD.https://www.frontiersin.org/articles/10.3389/fphar.2023.1102318/fullintervertebral disc degenerationmicrotubule stabilizationmechanical stressnucleus pulposusintervertebral disc
spellingShingle Xin Zhang
Shibin Shu
Zhenhua Feng
Yong Qiu
Hongda Bao
Zezhang Zhu
Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
Frontiers in Pharmacology
intervertebral disc degeneration
microtubule stabilization
mechanical stress
nucleus pulposus
intervertebral disc
title Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
title_full Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
title_fullStr Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
title_full_unstemmed Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
title_short Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
title_sort microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo yap pathway
topic intervertebral disc degeneration
microtubule stabilization
mechanical stress
nucleus pulposus
intervertebral disc
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1102318/full
work_keys_str_mv AT xinzhang microtubulestabilizationpromotesthesynthesisoftype2collageninnucleuspulposuscellbyactivatinghippoyappathway
AT shibinshu microtubulestabilizationpromotesthesynthesisoftype2collageninnucleuspulposuscellbyactivatinghippoyappathway
AT zhenhuafeng microtubulestabilizationpromotesthesynthesisoftype2collageninnucleuspulposuscellbyactivatinghippoyappathway
AT yongqiu microtubulestabilizationpromotesthesynthesisoftype2collageninnucleuspulposuscellbyactivatinghippoyappathway
AT hongdabao microtubulestabilizationpromotesthesynthesisoftype2collageninnucleuspulposuscellbyactivatinghippoyappathway
AT zezhangzhu microtubulestabilizationpromotesthesynthesisoftype2collageninnucleuspulposuscellbyactivatinghippoyappathway