Progranulin Protects Against Osteonecrosis of the Femoral Head by Activating ERK1/2 Pathway

被引：18

作者：

Han, Yingguang ^{[1
]}

Si, Meng ^{[1
]}

Zhao, Yunpeng ^{[1
]}

Liu, Yi ^{[1
]}

Cheng, Kaiyuan ^{[1
]}

Zhang, Yuedong ^{[2
]}

Jia, Jialin ^{[1
]}

Li, Jingkun ^{[3
]}

Nie, Lin ^{[1
]}

机构：

[1] Shandong Univ, Qilu Hosp, Dept Orthopaed Surg, 107,Wen Hua Xi Rd, Jinan 250012, Shandong, Peoples R China

[2] Taian Cent Hosp, Dept Orthopaed Surg, Tai An 271000, Shandong, Peoples R China

[3] Shandong Univ, Shandong Prov Qianfoshan Hosp, Dept Orthopaed Surg, 16766,Jingshi Rd, Jinan 250014, Shandong, Peoples R China

来源：

INFLAMMATION | 2017年 / 40卷 / 03期

关键词：

progranulin; osteonecrosis; ERK; TNF-alpha; GRANULIN-EPITHELIN PRECURSOR; EARLY-DIAGNOSIS; GROWTH-FACTOR; BONE; NECROSIS; EXPRESSION; MUTATIONS; ADAMTS-7; ELASTASE; TARGET;

D O I：

10.1007/s10753-017-0539-z

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The aim of this study was to investigate progranulin (PGRN) expression and its effect in cartilage degradation and in the pathogenesis of osteonecrosis of the femoral head (ONFH). Cartilage specimens were obtained from ONFH and FNF patients and PGRN expression was analyzed by immunohistochemistry, western blot analysis, and RT-PCR. Peripheral blood PGRN level was detected by ELISA. Additionally, primary chondrocytes were cultured and treated with PGRN. Next, the expression of aggrecan and collagen II and the activation of ERK1/2 were detected. We observed that the expression of PGRN was significantly upregulated in ONFH patients' articular cartilage, and recombinant PGRN could promote expression of aggrecan and collagen II and the activation of ERK1/2. Collectively, PGRN can improve chondrocyte anabolism and perform a therapeutic role in the pathogenesis of ONFH. This study helps to elucidate the pathogenesis of ONFH and presents PGRN as a potential target for the treatment of ONFH.

引用

页码：946 / 955

页数：10

共 33 条

[1] SKELETAL MANIFESTATIONS AND TREATMENT OF GAUCHERS DISEASE - REVIEW OF 20 CASES [J].

AMSTUTZ, HC ;

CAREY, EJ .

JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1966, A 48 (04) :670-&

[2] ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor [J].

Bai, Xiao-Hui ;

Wang, Da-Wei ;

Kong, Li ;

Zhang, Yan ;

Luan, Yi ;

Kobayashi, Tatsuya ;

Kronenberg, Henry M. ;

Yu, Xiu-Ping ;

Liu, Chuan-ju .

MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (15) :4201-4219

[3] Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease [J].

Baker, CA ;

Manuelidis, L .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (02) :675-679

[4] The granulin gene family: from cancer to dementia [J].

Bateman, Andrew ;

Bennett, Hugh P. J. .

BIOESSAYS, 2009, 31 (11) :1245-1254

[5] The epidemiology of osteonecrosis: findings from the GPRD and THIN databases in the UK [J].

Cooper, C. ;

Steinbuch, M. ;

Stevenson, R. ;

Miday, R. ;

Watts, N. B. .

OSTEOPOROSIS INTERNATIONAL, 2010, 21 (04) :569-577

[6]

CRUESS RL, 1975, CLIN ORTHOP RELAT R, P178

[7] Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21 [J].

Cruts, Marc ;

Gijselinck, Ilse ;

van der Zee, Julie ;

Engelborghs, Sebastiaan ;

Wils, Hans ;

Pirici, Daniel ;

Rademakers, Rosa ;

Vandenberghe, Rik ;

Dermaut, Bart ;

Martin, Jean-Jacques ;

van Duijn, Cornelia ;

Peeters, Karin ;

Sciot, Raf ;

Santens, Patrick ;

De Pooter, Tim ;

Mattheijssens, Maria ;

Van den Broeck, Marleen ;

Cuijt, Ivy ;

Vennekens, Krist'l ;

De Deyn, Peter P. ;

Kumar-Singh, Samir ;

Van Broeckhoven, Christine .

NATURE, 2006, 442 (7105) :920-924

[8]

CSUKA M, 1987, J RHEUMATOL, V14, P165

[9] Mutations in progranulin gene:: Clinical, pathological, and ribonucleic acid expression findings [J].

de Munain, Adolofo Lopez ;

Alzualde, Ainhoa ;

Gorostidi, Ana ;

Otaegui, David ;

Ruiz-Martinez, Javier ;

Indakoetxea, Begona ;

Ferrer, Isidro ;

Perez-Tur, Jordi ;

Saenz, Amets ;

Bergareche, Alberto ;

Barandiaran, Miriam ;

Poza, Juan Jose ;

Zabalza, Ramon ;

Ruiz, Irune ;

Urtasun, Miguel ;

Fernandez-Manchola, Inaki ;

Olasagasti, Bixen ;

Espinal, Juan Bautista ;

Olaskoaga, Javier ;

Ruibal, Marta ;

Moreno, Fermin ;

Carrera, Nieves ;

Masso, Jose Felix Marti .

BIOLOGICAL PSYCHIATRY, 2008, 63 (10) :946-952

[10] Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis [J].

Feng, Jian Q. ;

Guo, Feng-Jin ;

Jiang, Bai-Chun ;

Zhang, Yan ;

Frenkel, Sally ;

Wang, Da-Wei ;

Tang, Wei ;

Xie, Yixia ;

Liu, Chuan-Ju .

FASEB JOURNAL, 2010, 24 (06) :1879-1892

← 1 2 3 4 →