Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2014

Open Access 01-12-2014 | Research article

Dose-dependent regulation of cell proliferation and collagen degradation by estradiol on ligamentum flavum

Authors: Mei-Hsiu Chen, Chao-Kai Hu, Pei-Ru Chen, Yu-Shan Chen, Jui-Sheng Sun, Ming-Hong Chen

Published in: BMC Musculoskeletal Disorders | Issue 1/2014

Login to get access

Abstract

Background

Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum.

Methods

Primary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated.

Results

In our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17β-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10-9 M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol.

Conclusions

The results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum.
Appendix
Available only for authorised users
Literature
1.
Siebert E, Prüss H, Klingebiel R, Failli V, Einhäupl KM, Schwab JM: Lumbar spinal stenosis: syndrome, diagnostics and treatment. Nat Rev Neurol. 2009, 5: 392-403.CrossRefPubMed
2.
Kirkaldy-Willis WH, Paine KW, Cauchoix J, McIvor G: Lumbar spinal stenosis. Clin Orthop Relat Res. 1974, 99: 30-50.CrossRefPubMed
3.
Shafaq N, Suzuki A, Terai H, Wakitani S, Nakamura H: Cellularity and cartilage matrix increased in hypertrophied ligamentum flavum: histopathological analysis focusing on the mechanical stress and bone morphogenetic protein signaling. J Spinal Disord Tech. 2012, 25: 107-115.CrossRefPubMed
4.
Ishimoto Y, Yoshimura N, Muraki S, Yamada H, Nagata K, Hashizume H, Takiguchi N, Minamide A, Oka H, Kawaguchi H, Nakamura K, Akune T, Yoshida M: Prevalence of symptomatic lumbar spinal stenosis and its association with physical performance in a population-based cohort in Japan: the Wakayama spine study. Osteoarthr Cartil. 2012, 20: 1103-1108.CrossRefPubMed
5.
Matveeva N, Vrchakovski M: Lumbar Spinal Stenosis in Older Adults-Gender Differences. Maced J Med Sci. 2009, 2: 200-204.CrossRef
6.
Miyakoshi N, Itoi E, Murai H, Wakabayashi I, Ito H, Minato T: Inverse relation between osteoporosis and spondylosis in postmenopausal women as evaluated by bone mineral density and semiquantitative scoring of spinal degeneration. Spine. 2003, 28: 492-495.PubMed
7.
Evans JH, Nachemson AL: Biomechanical study of human lumbar ligamentum flavum. J Anat. 1969, 105: 188-189.PubMed
8.
Yahia LH, Garzon S, Strykowski H, Rivard CH: Ultrastructure of the human interspinous ligament and ligamentum flavum: a preliminary study. Spine. 1990, 15: 262-268.CrossRefPubMed
9.
Sairyo K, Biyani A, Goel V, Leaman D, Booth R, Thomas J, Gehling D, Vishnubhotla L, Long R, Ebraheim N: Pathomechanism of ligamentum flavum hypertrophy: a multidisciplinary investigation based on clinical, biomechanical, histologic, and biologic assessments. Spine. 2005, 30: 2649-2656.CrossRefPubMed
10.
Kosaka H, Sairyo K, Biyani A, Leaman D, Yeasting R, Higashino K, Sakai T, Katoh S, Sano T, Goel VK, Yasui N: Pathomechanism of loss of elasticity and hypertrophy of lumbar ligamentum flavum in elderly patients with lumbar spinal canal stenosis. Spine. 2007, 32: 2805-2811.CrossRefPubMed
11.
Brincat MP, Calleja-Agius J, Baron YM: The skin, carotid and intervertebral disc: making the connection!. Climacteric. 2007, 10 (Suppl 2): 83-87.CrossRefPubMed
12.
Calleja-Agius J, Muscat-Baron Y, Brincat MP: Estrogens and the intervertebral disc. Menopause Int. 2009, 15: 127-130.PubMed
13.
Hall G, Phillips TJ: Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol. 2005, 53: 555-568. quiz 569–72CrossRefPubMed
14.
Irie T, Takahata M, Majima T, Abe Y, Komatsu M, Iwasaki N, Minami A: Effect of selective estrogen receptor modulator/raloxifene analogue on proliferation and collagen metabolism of tendon fibroblast. Connect Tissue Res. 2010, 51: 179-187.CrossRefPubMed
15.
Nakada T, Kubota Y, Sasagawa I, Suzuki H, Watanabe M, Suzuki Y: The effect of oestradiol-17 beta on connective tissue protein in rat prostate. Int Urol Nephrol. 1994, 26: 327-335.CrossRefPubMed
16.
Natoli AK, Medley TL, Ahimastos AA, Drew BG, Thearle DJ, Dilley RJ, Kingwell BA: Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression. Hypertension. 2005, 46: 1129-1134.CrossRefPubMed
17.
Son ED, Lee JY, Lee S, Kim MS, Lee BG, Chang IS, Chung JH: Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating tgf-beta signaling in aged human skin in vivo. J Invest Dermatol. 2005, 124: 1149-1161.CrossRefPubMed
18.
Sanada H, Shikata J, Hamamoto H, Ueba Y, Yamamuro T, Takeda T: Changes in collagen cross-linking and lysyl oxidase by estrogen. Biochim Biophys Acta. 1978, 541: 408-413.CrossRefPubMed
19.
Lin G, Ning H, Wang G, Banie L, Lue TF, Lin C-S: Effects of birth trauma and estrogen on urethral elastic fibers and elastin expression. Urology. 2010, 76: 1018.e8–13-CrossRefPubMed
20.
Goupille P, Jayson MI, Valat JP, Freemont AJ: Matrix metalloproteinases: the clue to intervertebral disc degeneration?. Spine. 1998, 23: 1612-1626.CrossRefPubMed
21.
22.
23.
Woessner JF: Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991, 5: 2145-2154.PubMed
24.
Park J-B, Kong C-G, Suhl K-H, Chang E-D, Riew KD: The increased expression of matrix metalloproteinases associated with elastin degradation and fibrosis of the ligamentum flavum in patients with lumbar spinal stenosis. Clin Orthop Surg. 2009, 1: 81-89.CrossRefPubMedPubMedCentral
25.
26.
27.
Grohé C, Kahlert S, Löbbert K, Vetter H: Expression of oestrogen receptor alpha and beta in rat heart: role of local oestrogen synthesis. J Endocrinol. 1998, 156: R1-R7.CrossRefPubMed
28.
Cowley SM, Hoare S, Mosselman S, Parker MG: Estrogen receptors alpha and beta form heterodimers on DNA. J Biol Chem. 1997, 272: 19858-19862.CrossRefPubMed
29.
Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS: Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science. 1997, 277: 1508-1510.CrossRefPubMed
30.
Park J, Lee J, Park S, Riew K: Hypertrophy of Ligamentum Flavum in Lumbar Spinal Stenosis Associated with increased proteinase inhibitor concentration. J Bone Joint Surg. 2005, 87: 2750-2757.CrossRefPubMed
Metadata
Title
Dose-dependent regulation of cell proliferation and collagen degradation by estradiol on ligamentum flavum
Authors
Mei-Hsiu Chen
Chao-Kai Hu
Pei-Ru Chen
Yu-Shan Chen
Jui-Sheng Sun
Ming-Hong Chen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2014
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-15-238

Other articles of this Issue 1/2014

BMC Musculoskeletal Disorders 1/2014 Go to the issue

Research article

The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease

Research article

Evaluation of self-administered tests for pelvic girdle pain in pregnancy

Research article

Reproducibility of and sex differences in common orthopaedic ankle and foot tests in runners

Research article

Fractures are increased and bisphosphonate use decreased in individuals with insulin-dependent diabetes: a 10 year cohort study

Research article

The cn/cn dwarf mouse. Histomorphometric, ultrastructural, and radiographic study in mutants corresponding to human acromesomelic dysplasia Maroteaux type (AMDM)

Case report

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) presenting as diffuse myositis