低强度脉冲聚焦超声通过上调PGAM5蛋白表达促进软骨细胞线粒体自噬

叶海霞; 虞乐华; 贾朗

doi:10.16016/j.1000-5404.202009202

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低强度脉冲聚焦超声通过上调PGAM5蛋白表达促进软骨细胞线粒体自噬

基础医学 | 更新时间：2026-01-09

- 低强度脉冲聚焦超声通过上调PGAM5蛋白表达促进软骨细胞线粒体自噬
- Focused low-intensity pulsed ultrasound promotes chondrocyte mitophagy via up-regulating PGAM5 protein
- 第三军医大学学报 2021年43卷第5期页码：403-410
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金青年科学基金(81802234)
- DOI：10.16016/j.1000-5404.202009202
  中图分类号：
- 收稿：2020-09-23，
  
  纸质出版：2021-03-15
- 稿件说明：
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叶海霞, 虞乐华, 贾朗. 低强度脉冲聚焦超声通过上调PGAM5蛋白表达促进软骨细胞线粒体自噬[J]. 第三军医大学学报, 2021,43(5):403-410.

Haixia YE, Lehua YU, Lang JIA. Focused low-intensity pulsed ultrasound promotes chondrocyte mitophagy via up-regulating PGAM5 protein[J]. Journal of Third Military Medical University, 2021, 43(5): 403-410.
叶海霞, 虞乐华, 贾朗. 低强度脉冲聚焦超声通过上调PGAM5蛋白表达促进软骨细胞线粒体自噬[J]. 第三军医大学学报, 2021,43(5):403-410. DOI： 10.16016/j.1000-5404.202009202.

Haixia YE, Lehua YU, Lang JIA. Focused low-intensity pulsed ultrasound promotes chondrocyte mitophagy via up-regulating PGAM5 protein[J]. Journal of Third Military Medical University, 2021, 43(5): 403-410. DOI： 10.16016/j.1000-5404.202009202.

摘要

Abstract

Objective

To investigate the effect of focused low-intensity pulsed ultrasound (FLIPUS) on the activation of mitophagy in chondrocytes.

Methods

Chondrocytes were isolated from the knee articular cartilage of C57BL/6J suckling mice

and then primarily cultured. Then osteoarthritis-like chondrocyte injury was inflicted by IL-1β simulation in the chondrocytes and identified. The chondrocytes were divided into 3 groups

that is

control

IL-1β and IL-1β+FLIPUS group. The mRNA expression of Col2α1 and MMP13 was detected by quantitative real-time PCR

and the protein levels of Col2α1

MMP13

LC3B-Ⅱ

TOM20

TIM23

PGAM5

FUNDC1 and p-FUNDC1 (p-ser13) were detected by Western blotting.

Results

We cultured primary chondrocytes and established osteoarthritis-like chondrocyte injury model successfully. Compared with the control group

the mRNA and protein levels of Col2α1 were significantly decreased (

0.01)

while the levels of MMP13 were significantly increased (

0.01) in the IL-1β group. The levels of Col2α1 were obviously enhanced (

0.05)

while those of MMP13 were reduced (

0.01) in the IL-1β+FLIPUS group than the IL-1β group. Compared with the control group

the protein expression of LC3B-Ⅱ was remarkably reduced in the IL-1β group (

0.05). The protein levels of LC3B-Ⅱ and PGAM5 were significantly increased (

0.01)

while those of TOM20

TIM23 and p-Ser13 were

notably decreased (

0.05) in the IL-1β+FLIPUS group than the IL-1β group.

Conclusion

FLIPUS may activate the mitophagy in chondrocytes though dephosphorylation of FUNDC1 Ser13

via

up-regulating PGAM5 expression.

关键词

Keywords

references

JIA L WANG Y CHEN J Y Efficacy of focused low-intensity pulsed ultrasound therapy for the management of knee osteoarthritis: a randomized, double blind, placebo-controlled trial Sci Rep 2016 6 35453 10.1038/srep35453 JIA L, WANG Y, CHEN J Y, et al . Efficacy of focused low-intensity pulsed ultrasound therapy for the management of knee osteoarthritis: a randomized, double blind, placebo-controlled trial[J ] . Sci Rep, 2016, 6: 35453. DOI:10.1038/srep35453.

贾朗谭波涛陈锦云低强度脉冲聚焦超声治疗膝骨关节炎的安全性和有效性上海交通大学学报(医学版) 2020 40 5 633 638 10.3969/j.issn.1674-8115.2020.05.011 贾朗, 谭波涛, 陈锦云. 低强度脉冲聚焦超声治疗膝骨关节炎的安全性和有效性[J]. 上海交通大学学报(医学版), 2020, 40(5): 633-638. DOI:10.3969/j.issn.1674-8115.2020.05.011.

JIA L TAN B T CHEN J Y Safety and efficacy of focused low-intensity pulsed ultrasound therapy for the treatment of knee osteoarthritis J Shanghai Jiaotong Univ(Med Sci) 2020 40 5 633 638 10.3969/j.issn.1674-8115.2020.05.011 JIA L, TAN B T, CHEN J Y. Safety and efficacy of focused low-intensity pulsed ultrasound therapy for the treatment of knee osteoarthritis[J]. J Shanghai Jiaotong Univ(Med Sci), 2020, 40(5): 633-638. DOI:10.3969/j.issn.1674-8115.2020.05.011.

JIA L CHEN J Y WANG Y Focused low-intensity pulsed ultrasound affects extracellular matrix degradation via decreasing chondrocyte apoptosis and inflammatory mediators in a surgically induced osteoarthritic rabbit model Ultrasound Med Biol 2016 42 1 208 219 10.1016/j.ultrasmedbio.2015.08.010 JIA L, CHEN J Y, WANG Y, et al . Focused low-intensity pulsed ultrasound affects extracellular matrix degradation via decreasing chondrocyte apoptosis and inflammatory mediators in a surgically induced osteoarthritic rabbit model[J ] . Ultrasound Med Biol, 2016, 42(1): 208-219. DOI:10.1016/j.ultrasmedbio.2015.08.010.

WANG S DENG Z MA Y The role of autophagy and mitophagy in bone metabolic disorders Int J Biol Sci 2020 16 14 2675 2691 10.7150/ijbs.46627 WANG S, DENG Z, MA Y, et al . The role of autophagy and mitophagy in bone metabolic disorders[J ] . Int J Biol Sci, 2020, 16(14): 2675-2691. DOI:10.7150/ijbs.46627.

LÓPEZ DE FIGUEROA P LOTZ M K BLANCO F J Autophagy activation and protection from mitochondrial dysfunction in human chondrocytes Arthritis Rheumatol 2015 67 4 966 976 10.1002/art.39025 LÓPEZ DE FIGUEROA P, LOTZ M K, BLANCO F J, et al . Autophagy activation and protection from mitochondrial dysfunction in human chondrocytes[J ] . Arthritis Rheumatol, 2015, 67(4): 966-976. DOI:10.1002/art.39025.

ROCKEL J S KAPOOR M Autophagy: controlling cell fate in rheumatic diseases Nat Rev Rheumatol 2016 12 9 517 531 10.1038/nrrheum.2016.92 ROCKEL J S, KAPOOR M. Autophagy: controlling cell fate in rheumatic diseases[J]. Nat Rev Rheumatol, 2016, 12(9): 517-531. DOI:10.1038/nrrheum.2016.92.

LINDAHL O Clinical effect of ultrasonic waves in chondromalacic and osteoarthritic changes in the knee Rheumatism 1952 8 2 36 37 http://www.ncbi.nlm.nih.gov/pubmed/14942226 LINDAHL O. Clinical effect of ultrasonic waves in chondromalacic and osteoarthritic changes in the knee[J]. Rheumatism, 1952, 8(2): 36-37.

LOYOLA-SÁNCHEZ A RICHARDSON J MACINTYRE N J Efficacy of ultrasound therapy for the management of knee osteoarthritis: a systematic review with meta-analysis Osteoarthritis Cartilage 2010 18 9 1117 1126 10.1016/j.joca.2010.06.010 LOYOLA-SÁNCHEZ A, RICHARDSON J, MACINTYRE N J. Efficacy of ultrasound therapy for the management of knee osteoarthritis: a systematic review with meta-analysis[J]. Osteoarthritis Cartilage, 2010, 18(9): 1117-1126. DOI:10.1016/j.joca.2010.06.010.

ULUS Y TANDER B AKYOL Y Therapeutic ultrasound versus sham ultrasound for the management of patients with knee osteoarthritis: a randomized double-blind controlled clinical study Int J Rheum Dis 2012 15 2 197 206 10.1111/j.1756-185x.2012.01709.x ULUS Y, TANDER B, AKYOL Y, et al . Therapeutic ultrasound versus sham ultrasound for the management of patients with knee osteoarthritis: a randomized double-blind controlled clinical study[J ] . Int J Rheum Dis, 2012, 15(2): 197-206. DOI:10.1111/j.1756-185x.2012.01709.x.

CAKIR S HEPGULER S OZTURK C Efficacy of therapeutic ultrasound for the management of knee osteoarthritis Am J Phys Med Rehabil 2014 93 5 405 412 10.1097/phm.0000000000000033 CAKIR S, HEPGULER S, OZTURK C, et al . Efficacy of therapeutic ultrasound for the management of knee osteoarthritis[J ] . Am J Phys Med Rehabil, 2014, 93(5): 405-412. DOI:10.1097/phm.0000000000000033.

MCALINDON T E BANNURU R R SULLIVAN M C OARSI guidelines for the non-surgical management of knee osteoarthritis Osteoarthr Cartil 2014 22 3 363 388 10.1016/j.joca.2014.01.003 MCALINDON T E, BANNURU R R, SULLIVAN M C, et al . OARSI guidelines for the non-surgical management of knee osteoarthritis[J ] . Osteoarthr Cartil, 2014, 22(3): 363-388. DOI:10.1016/j.joca.2014.01.003.

OZGÖNENEL L AYTEKIN E DURMUŞOGLU G A double-blind trial of clinical effects of therapeutic ultrasound in knee osteoarthritis Ultrasound Med Biol 2009 35 1 44 49 10.1016/j.ultrasmedbio.2008.07.009 OZGÖNENEL L, AYTEKIN E, DURMUŞOGLU G. A double-blind trial of clinical effects of therapeutic ultrasound in knee osteoarthritis[J]. Ultrasound Med Biol, 2009, 35(1): 44-49. DOI:10.1016/j.ultrasmedbio.2008.07.009.

HUANG M H LIN Y S LEE C L Use of ultrasound to increase effectiveness of isokinetic exercise for knee osteoarthritis Arch Phys Med Rehabil 2005 86 8 1545 1551 10.1016/j.apmr.2005.02.007 HUANG M H, LIN Y S, LEE C L, et al . Use of ultrasound to increase effectiveness of isokinetic exercise for knee osteoarthritis[J ] . Arch Phys Med Rehabil, 2005, 86(8): 1545-1551. DOI:10.1016/j.apmr.2005.02.007.

周崑周伟陈文直低强度脉冲超声对美蓝渗入正常兔膝关节软骨的作用重庆医科大学学报 2012 37 2 121 124 https://www.cnki.com.cn/Article/CJFDTOTAL-ZQYK201202009.htm 周崑, 周伟, 陈文直, 等. 低强度脉冲超声对美蓝渗入正常兔膝关节软骨的作用[J]. 重庆医科大学学报, 2012, 37(2): 121-124.

ZHOU K ZHOU W CHEN W Z Low intensity pulsed ultrasound for promoting penetration of methylene blue into knee cartilage of normal rabbit J Chongqing Med Univ 2012 37 2 121 124 https://www.cnki.com.cn/Article/CJFDTOTAL-ZQYK201202009.htm ZHOU K, ZHOU W, CHEN W Z, et al . Low intensity pulsed ultrasound for promoting penetration of methylene blue into knee cartilage of normal rabbit[J ] . J Chongqing Med Univ, 2012, 37(2): 121-124.

ATKINS T J DUCK F A Heating caused by selected pulsed Doppler and physiotherapy ultrasound beams measured using thermal test objects Eur J Ultrasound 2003 16 3 243 252 10.1016/s0929-8266(02)00079-4 ATKINS T J, DUCK F A. Heating caused by selected pulsed Doppler and physiotherapy ultrasound beams measured using thermal test objects[J]. Eur J Ultrasound, 2003, 16(3): 243-252. DOI:10.1016/s0929-8266(02)00079-4.

PANDIT R LEINENGA G GÖTZ J Repeated ultrasound treatment of tau transgenic mice clears neuronal tau by autophagy and improves behavioral functions Theranostics 2019 9 13 3754 3767 10.7150/thno.34388 PANDIT R, LEINENGA G, GÖTZ J. Repeated ultrasound treatment of tau transgenic mice clears neuronal tau by autophagy and improves behavioral functions[J]. Theranostics, 2019, 9(13): 3754-3767. DOI:10.7150/thno.34388.

ZHANG B CHEN H G OUYANG J J SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1β and contributes to LIPUS-mediated anti-inflammatory effect Autophagy 2020 16 7 1262 1278 10.1080/15548627.2019.1664705 ZHANG B, CHEN H G, OUYANG J J, et al . SQSTM1-dependent autophagic degradation of PKM2 inhibits the production of mature IL1B/IL-1β and contributes to LIPUS-mediated anti-inflammatory effect[J ] . Autophagy, 2020, 16(7): 1262-1278. DOI:10.1080/15548627.2019.1664705.

ZHOU H Y LI Q WANG J X Low-intensity pulsed ultrasound repair in mandibular condylar cartilage injury rabbit model Arch Oral Biol 2019 104 60 66 10.1016/j.archoralbio.2019.05.018 ZHOU H Y, LI Q, WANG J X, et al . Low-intensity pulsed ultrasound repair in mandibular condylar cartilage injury r abbit model[J ] . Arch Oral Biol, 2019, 104:60-66.DOI:10.1016/j.archoralbio.2019.05.018.

MILNER P I FAIRFAX T P A BROWNING J A The effect of O2 tension on pH homeostasis in equine articular chondrocytes Arthritis Rheum 2006 54 11 3523 3532 10.1002/art.22209 MILNER P I, FAIRFAX T P A, BROWNING J A, et al . The effect of O2 tension on pH homeostasis in equine articular chondrocytes[J ] . Arthritis Rheum, 2006, 54(11): 3523-3532. DOI:10.1002/art.22209.

ZHANG F J LUO W LEI G H Role of HIF-1α and HIF-2α in osteoarthritis Joint Bone Spine 2015 82 3 144 147 10.1016/j.jbspin.2014.10.003 ZHANG F J, LUO W, LEI G H. Role of HIF-1α and HIF-2α in osteoarthritis[J]. Joint Bone Spine, 2015, 82(3): 144-147.DOI:10.1016/j.jbspin.2014.10.003.

HU S ZHANG C NI L Stabilization of HIF-1α alleviates osteoarthritis via enhancing mitophagy Cell Death Dis 2020 11 6 481 10.1038/s41419-020-2680-0 HU S, ZHANG C, NI L, et al . Stabilization of HIF-1α alleviates osteoarthritis via enhancing mitophagy[J ] . Cell Death Dis, 2020, 11(6): 481. DOI:10.1038/s41419-020-2680-0.

LIU L FENG D CHEN G Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells Nat Cell Biol 2012 14 2 177 185 10.1038/ncb2422 LIU L, FENG D, CHEN G, et al . Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells[J ] . Nat Cell Biol, 2012, 14(2): 177-185. DOI:10.1038/ncb2422.

CHEN G HAN Z FENG D A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy Mol Cell 2014 54 3 362 377 10.1016/j.molcel.2014.02.034 CHEN G, HAN Z, FENG D, et al . A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy[J ] . Mol Cell, 2014, 54(3): 362-377. DOI: 10.1016/j.molcel.2014.02.034.

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