Skip to main content
Erschienen in: Advances in Therapy 1/2020

21.11.2019 | Original Research

Expression of HSPA8 in Nucleus Pulposus of Lumbar Intervertebral Disc and Its Effect on Degree of Degeneration

verfasst von: Yong Liu, Hua-Cong Wang, Hong-Fei Xiang, Cang-Hai Jin, Bo-Hua Chen

Erschienen in: Advances in Therapy | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Abstract

Introduction

This study aimed to investigate the expression of a 70-kDa heat shock protein [heat shock 70-kDa protein 8 (HSPA8)/heat shock protein 70 (Hsc70)] in human degenerative lumbar intervertebral discs and its relationship with the degree of degeneration of human intervertebral discs.

Methods

A total of 72 cases of lumbar intervertebral disc nucleus pulposus tissues were collected. Among these, 18 cases of nucleus pulposus tissue were assigned to the control group, while 54 cases of nucleus pulposus tissues were assigned to the experimental group. According to the preoperative MRI, cases in the experimental group were further divided into three groups: protrusion group (n = 18), extrusion group (n = 18), and sequestration group (n = 18). Western blot was performed to determine the relative expression of HSPA8 in the nucleus pulposus in each group. Hematoxylin and eosin staining was performed to determine the number of nucleus pulposus cells, morphological differences, and cell densities of the degenerated intervertebral discs and normal intervertebral discs. Immunohistochemistry was performed to determine the expression of HSPA8 in nucleus pulposus tissues in each group.

Results

Hematoxylin and eosin staining results: There were significant differences in cell morphology and number between the control group and the experimental group. Furthermore, there were significant differences in cell density (F = 936.80, P < 0.01). Immunohistochemistry results: HSPA8 was expressed in lumbar intervertebral disc nucleus pulposus tissues, and its expression of gradually decreased with the severity of the disease, and the differences were significant (F = 2110.43, P < 0.01). Western blot results: The expression of HSPA8 in human degenerative nucleus pulposus tissues gradually decreased, and the differences were significant (F = 1841.72, P < 0.01).

Conclusion

HSPA8 is stably expressed in human intervertebral disc nucleus pulposus tissues, and its expression is associated with the degree of intervertebral disc degeneration.
Literatur
1.
Zurück zum Zitat Feng C, Liu H, Yang Y, Huang B, Zhou Y. Growth and differentiation factor-5 contributes to the structural and functional maintenance of the intervertebral disc. Cell Physiol Biochem. 2015;35:1–16.CrossRef Feng C, Liu H, Yang Y, Huang B, Zhou Y. Growth and differentiation factor-5 contributes to the structural and functional maintenance of the intervertebral disc. Cell Physiol Biochem. 2015;35:1–16.CrossRef
2.
Zurück zum Zitat Blanquer SB, Grijpma DW, Poot AA. Delivery systems for the treatment of degenerated intervertebral discs. Adv Drug Deliv Rev. 2015;84:172–87.CrossRef Blanquer SB, Grijpma DW, Poot AA. Delivery systems for the treatment of degenerated intervertebral discs. Adv Drug Deliv Rev. 2015;84:172–87.CrossRef
3.
Zurück zum Zitat Ma CJ, Luo SS, Li JS, Cao HJ, An ZW, Zhang X. Role of HIF in the pathology mechanism of the herniation of lumbar intervertebral disc. Anhui Med Pharm J. 2017;21:1306–10. Ma CJ, Luo SS, Li JS, Cao HJ, An ZW, Zhang X. Role of HIF in the pathology mechanism of the herniation of lumbar intervertebral disc. Anhui Med Pharm J. 2017;21:1306–10.
4.
Zurück zum Zitat Ohashi M, Watanabe K, Hirano T, Hasegawa K, Katsumi K, Shoji H, Mizouchi T, Endo N. Predicting factors at skeletal maturity for curve progression and low back pain in adult patients treated nonoperatively for adolescent idiopathic scoliosis with thoracolumbar/lumbar curves: a mean 25-year follow-up. Spine (Phila Pa 1976). 2018;43:E1403–11.CrossRef Ohashi M, Watanabe K, Hirano T, Hasegawa K, Katsumi K, Shoji H, Mizouchi T, Endo N. Predicting factors at skeletal maturity for curve progression and low back pain in adult patients treated nonoperatively for adolescent idiopathic scoliosis with thoracolumbar/lumbar curves: a mean 25-year follow-up. Spine (Phila Pa 1976). 2018;43:E1403–11.CrossRef
5.
Zurück zum Zitat Matsui H, Kanamori M, Ishihara H, Yudoh K, Naruse Y, Tsuji H. Familial predisposition for lumbar degenerative disc disease. A case-control study. Spine (Phila Pa 1976). 1998;23:1029–34.CrossRef Matsui H, Kanamori M, Ishihara H, Yudoh K, Naruse Y, Tsuji H. Familial predisposition for lumbar degenerative disc disease. A case-control study. Spine (Phila Pa 1976). 1998;23:1029–34.CrossRef
6.
Zurück zum Zitat Ala-Kokko L. Genetic risk factors for lumbar disc disease. Ann Med. 2002;34:42–7.CrossRef Ala-Kokko L. Genetic risk factors for lumbar disc disease. Ann Med. 2002;34:42–7.CrossRef
7.
Zurück zum Zitat Schistad EI, Bjorland S, Røe C, Gjerstad J, Vetti N, Myhre K, Espeland A. Five-year development of lumbar disc degeneration-a prospective study. Skelet Radiol. 2019;48:871–9.CrossRef Schistad EI, Bjorland S, Røe C, Gjerstad J, Vetti N, Myhre K, Espeland A. Five-year development of lumbar disc degeneration-a prospective study. Skelet Radiol. 2019;48:871–9.CrossRef
8.
Zurück zum Zitat Song YQ, Karasugi T, Cheung KM, Chiba K, Ho DW, Miyake A, Kao PY, Sze KL, Yee A, Takahashi A, Kawaguchi Y, Mikami Y, Matsumoto M, Togawa D, Kanayama M, Shi D, Dai J, Jiang Q, Wu C, Tian W, Wang N, Leong JC, Luk KD, Yip SP, Cherny SS, Wang J, Mundlos S, Kelempisioti A, Eskola PJ, Männikkö M, Mäkelä P, Karppinen J, Järvelin MR, O’Reilly PF, Kubo M, Kimura T, Kubo T, Toyama Y, Mizuta H, Cheah KS, Tsunoda T, Sham PC, Ikegawa S, Chan D. Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. J Clin Investig. 2013;123:4909–17.CrossRef Song YQ, Karasugi T, Cheung KM, Chiba K, Ho DW, Miyake A, Kao PY, Sze KL, Yee A, Takahashi A, Kawaguchi Y, Mikami Y, Matsumoto M, Togawa D, Kanayama M, Shi D, Dai J, Jiang Q, Wu C, Tian W, Wang N, Leong JC, Luk KD, Yip SP, Cherny SS, Wang J, Mundlos S, Kelempisioti A, Eskola PJ, Männikkö M, Mäkelä P, Karppinen J, Järvelin MR, O’Reilly PF, Kubo M, Kimura T, Kubo T, Toyama Y, Mizuta H, Cheah KS, Tsunoda T, Sham PC, Ikegawa S, Chan D. Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. J Clin Investig. 2013;123:4909–17.CrossRef
9.
Zurück zum Zitat Zhang WQ, Jiang J, Pang XD, et al. Mechanism of lumbar disc degeneration. Chin J Orthop. 2008;21:1635–6. Zhang WQ, Jiang J, Pang XD, et al. Mechanism of lumbar disc degeneration. Chin J Orthop. 2008;21:1635–6.
10.
Zurück zum Zitat Yaltirik CK, Timirci-Kahraman Ö, Gulec-Yilmaz S, Ozdogan S, Atalay B, Isbir T. The evaluation of proteoglycan levels and the possible role of gene (c.6423T > C) variant in patients with lumbar disc degeneration disease. In Vivo. 2019;33:413–7.CrossRef Yaltirik CK, Timirci-Kahraman Ö, Gulec-Yilmaz S, Ozdogan S, Atalay B, Isbir T. The evaluation of proteoglycan levels and the possible role of gene (c.6423T > C) variant in patients with lumbar disc degeneration disease. In Vivo. 2019;33:413–7.CrossRef
11.
Zurück zum Zitat Lamian V, Small GM, Feldherr CM. Evidence for the existence of a novel mechanism for the nuclear import of Hsc70. Exp Cell Res. 1996;228:84–91.CrossRef Lamian V, Small GM, Feldherr CM. Evidence for the existence of a novel mechanism for the nuclear import of Hsc70. Exp Cell Res. 1996;228:84–91.CrossRef
13.
Zurück zum Zitat Bi X, Xu M, Li J, Huang T, Jiang B, Shen L, Luo L, Liu S, Yin Z. Heat shock protein 27 inhibits HMGB1 translocation by regulating CBP acetyltransferase activity and ubiquitination. Mol Immunol. 2019;108:45–55.CrossRef Bi X, Xu M, Li J, Huang T, Jiang B, Shen L, Luo L, Liu S, Yin Z. Heat shock protein 27 inhibits HMGB1 translocation by regulating CBP acetyltransferase activity and ubiquitination. Mol Immunol. 2019;108:45–55.CrossRef
14.
Zurück zum Zitat Hunt C, Morimoto RI. Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc Natl Acad Sci USA. 1985;82:6455–9.CrossRef Hunt C, Morimoto RI. Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc Natl Acad Sci USA. 1985;82:6455–9.CrossRef
15.
Zurück zum Zitat Liu T, Daniels CK, Cao S. Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential. Pharmacol Ther. 2012;136:354–74.CrossRef Liu T, Daniels CK, Cao S. Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential. Pharmacol Ther. 2012;136:354–74.CrossRef
16.
Zurück zum Zitat Kityk R, Kopp J, Sinning I, Mayer MP. Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones. Mol Cell. 2012;48:863–74.CrossRef Kityk R, Kopp J, Sinning I, Mayer MP. Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones. Mol Cell. 2012;48:863–74.CrossRef
17.
Zurück zum Zitat Loeffler DA, Klaver AC, Coffey MP, Aasly JO, LeWitt PA. Age-related decrease in heat shock 70-kDa protein 8 in cerebrospinal fluid is associated with increased oxidative stress. Front Aging Neurosci. 2016;8:178.CrossRef Loeffler DA, Klaver AC, Coffey MP, Aasly JO, LeWitt PA. Age-related decrease in heat shock 70-kDa protein 8 in cerebrospinal fluid is associated with increased oxidative stress. Front Aging Neurosci. 2016;8:178.CrossRef
18.
Zurück zum Zitat Ye D, Liang W, Dai L, Zhou L, Yao Y, Zhong X, Chen H, Xu J. Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells. Clin Exp Pharmacol Physiol. 2015;42:530–6.CrossRef Ye D, Liang W, Dai L, Zhou L, Yao Y, Zhong X, Chen H, Xu J. Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells. Clin Exp Pharmacol Physiol. 2015;42:530–6.CrossRef
19.
Zurück zum Zitat Spengler DM. Lumbar discectomy Results with limited disc excision and selective foraminotomy. Spine (Phila Pa 1976). 1982;7:604–7.CrossRef Spengler DM. Lumbar discectomy Results with limited disc excision and selective foraminotomy. Spine (Phila Pa 1976). 1982;7:604–7.CrossRef
20.
Zurück zum Zitat Vadalà G, Russo F, Di Martino A, Denaro V. Intervertebral disc regeneration: from the degenerative cascade to molecular therapy and tissue engineering. J Tissue Eng Regen Med. 2015;9:679–90.CrossRef Vadalà G, Russo F, Di Martino A, Denaro V. Intervertebral disc regeneration: from the degenerative cascade to molecular therapy and tissue engineering. J Tissue Eng Regen Med. 2015;9:679–90.CrossRef
21.
Zurück zum Zitat Gornet MG, Peacock J, Claude J, Schranck FW, Copay AG, Eastlack RK, Benz R, Olshen A, Lotz JC. Magnetic resonance spectroscopy (MRS) can identify painful lumbar discs and may facilitate improved clinical outcomes of lumbar surgeries for discogenic pain. Eur Spine J. 2019;28:674–87.CrossRef Gornet MG, Peacock J, Claude J, Schranck FW, Copay AG, Eastlack RK, Benz R, Olshen A, Lotz JC. Magnetic resonance spectroscopy (MRS) can identify painful lumbar discs and may facilitate improved clinical outcomes of lumbar surgeries for discogenic pain. Eur Spine J. 2019;28:674–87.CrossRef
22.
Zurück zum Zitat Zehra U, Cheung JPY, Bow C, Lu W, Samartzis D. Multidimensional vertebral endplate defects are associated with disc degeneration, Modic changes, facet joint abnormalities and pain. J Orthop Res. 2019;37:1080–9.CrossRef Zehra U, Cheung JPY, Bow C, Lu W, Samartzis D. Multidimensional vertebral endplate defects are associated with disc degeneration, Modic changes, facet joint abnormalities and pain. J Orthop Res. 2019;37:1080–9.CrossRef
23.
Zurück zum Zitat Stricher F, Macri C, Ruff M, Muller S. HSPA8/HSC70 chaperone protein: structure, function, and chemical targeting. Autophagy. 2013;9:1937–54.CrossRef Stricher F, Macri C, Ruff M, Muller S. HSPA8/HSC70 chaperone protein: structure, function, and chemical targeting. Autophagy. 2013;9:1937–54.CrossRef
24.
Zurück zum Zitat Goldfarb SB, Kashlan OB, Watkins JN, Suaud L, Yan W, Kleyman TR, Rubenstein RC. Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels. Proc Natl Acad Sci USA. 2006;103:5817–22.CrossRef Goldfarb SB, Kashlan OB, Watkins JN, Suaud L, Yan W, Kleyman TR, Rubenstein RC. Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels. Proc Natl Acad Sci USA. 2006;103:5817–22.CrossRef
25.
Zurück zum Zitat Deane EE, Woo NY. Impact of heavy metals and organochlorines on hsp70 and hsc70 gene expression in black sea bream fibroblasts. Aquat Toxicol. 2006;79:9–15.CrossRef Deane EE, Woo NY. Impact of heavy metals and organochlorines on hsp70 and hsc70 gene expression in black sea bream fibroblasts. Aquat Toxicol. 2006;79:9–15.CrossRef
26.
Zurück zum Zitat Geraci F, Pinsino A, Turturici G, Savona R, Giudice G, Sconzo G. Nickel, lead, and cadmium induce differential cellular responses in sea urchin embryos by activating the synthesis of different HSP70s. Biochem Biophys Res Commun. 2004;322:873–7.CrossRef Geraci F, Pinsino A, Turturici G, Savona R, Giudice G, Sconzo G. Nickel, lead, and cadmium induce differential cellular responses in sea urchin embryos by activating the synthesis of different HSP70s. Biochem Biophys Res Commun. 2004;322:873–7.CrossRef
27.
Zurück zum Zitat Makino H, Seki S, Yahara Y, Shiozawa S, Aikawa Y, Motomura H, Nogami M, Watanabe K, Sainoh T, Ito H, Tsumaki N, Kawaguchi Y, Yamazaki M, Kimura T. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain. Sci Rep. 2017;7:16983.CrossRef Makino H, Seki S, Yahara Y, Shiozawa S, Aikawa Y, Motomura H, Nogami M, Watanabe K, Sainoh T, Ito H, Tsumaki N, Kawaguchi Y, Yamazaki M, Kimura T. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain. Sci Rep. 2017;7:16983.CrossRef
28.
Zurück zum Zitat Jiang PF, Ma ZW, Zhang MZ, Deng YJ. Expression of ADAMTS-7 and its mechanism in patients with degenerative changes in lumbar intervertebral disc. Pract J Clin Med. 2017;14:101–4. Jiang PF, Ma ZW, Zhang MZ, Deng YJ. Expression of ADAMTS-7 and its mechanism in patients with degenerative changes in lumbar intervertebral disc. Pract J Clin Med. 2017;14:101–4.
29.
Zurück zum Zitat Nikolaou G, Zibis AH, Fyllos AH, Katsioulis A, Sotiriou S, Kotrotsios A, Sgantzos M, Vassiou A, Arvanitis DL. Detection of O-Linked-N-Acetylglucosamine modification and its associated enzymes in human degenerated intervertebral discs. Asian Spine J. 2017;11:863–9.CrossRef Nikolaou G, Zibis AH, Fyllos AH, Katsioulis A, Sotiriou S, Kotrotsios A, Sgantzos M, Vassiou A, Arvanitis DL. Detection of O-Linked-N-Acetylglucosamine modification and its associated enzymes in human degenerated intervertebral discs. Asian Spine J. 2017;11:863–9.CrossRef
30.
Zurück zum Zitat Johnson ZI, Gogate SS, Day R, Binch A, Markova DZ, Chiverton N, Cole A, Conner M, Shapiro IM, Le Maitre CL, Risbud MV. Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: novel HIF-1-mediated regulation of aquaporins in NP cells. Oncotarget. 2015;6:11945–58.PubMedPubMedCentral Johnson ZI, Gogate SS, Day R, Binch A, Markova DZ, Chiverton N, Cole A, Conner M, Shapiro IM, Le Maitre CL, Risbud MV. Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: novel HIF-1-mediated regulation of aquaporins in NP cells. Oncotarget. 2015;6:11945–58.PubMedPubMedCentral
Metadaten
Titel
Expression of HSPA8 in Nucleus Pulposus of Lumbar Intervertebral Disc and Its Effect on Degree of Degeneration
verfasst von
Yong Liu
Hua-Cong Wang
Hong-Fei Xiang
Cang-Hai Jin
Bo-Hua Chen
Publikationsdatum
21.11.2019
Verlag
Springer Healthcare
Erschienen in
Advances in Therapy / Ausgabe 1/2020
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-019-01136-9

Weitere Artikel der Ausgabe 1/2020

Advances in Therapy 1/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.