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 ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2016

Open Access 01-12-2016 | Research article

The tenocyte phenotype of human primary tendon cells in vitro is reduced by glucocorticoids

Authors: Christoph Spang, Jialin Chen, Ludvig J. Backman

Published in: BMC Musculoskeletal Disorders | Issue 1/2016

Login to get access

Abstract

Background

The use of corticosteroids (e.g., dexamethasone) as treatment for tendinopathy has recently been questioned as higher risks for ruptures have been observed clinically. In vitro studies have reported that dexamethasone exposed tendon cells, tenocytes, show reduced cell viability and collagen production. Little is known about the effect of dexamethasone on the characteristics of tenocytes. Furthermore, there are uncertainties about the existence of apoptosis and if the reduction of collagen affects all collagen subtypes.

Methods

We evaluated these aspects by exposing primary tendon cells to dexamethasone (Dex) in concentrations ranging from 1 to 1000 nM. Gene expression of the specific tenocyte markers scleraxis (Scx) and tenomodulin (Tnmd) and markers for other mesenchymal lineages, such as bone (Alpl, Ocn), cartilage (Acan, Sox9) and fat (Cebpα, Pparg) was measured via qPCR. Cell viability and proliferation was calculated using a MTS Assay. Cell death was measured by LDH assay and cleaved caspase-3 using Western Blot. Gene expression of collagen subtypes Col1, Col3 and Col14 was analyzed using qPCR.

Results

Stimulation with Dex decreased cell viability and LDH levels. Dex also induced a significant reduction of Scx gene expression and a marked loss of fibroblast like cell shape. The mRNA for all examined collagen subtypes was found to be down-regulated. Among non-tendinous genes only Pparg was significantly increased, whereas Acan, Alpl and Sox9 were reduced.

Conclusions

These results indicate a Dex induced phenotype drift of the tenocytes by reducing scleraxis expression. Reduction of several collagen subtypes, but not cell death, seems to be a feature of Dex induced tissue degeneration.
Literature
1.
Rolf C, Movin T. Etiology, histopathology, and outcome of surgery in achillodynia. Foot Ankle Int. 1997;18:565–9.CrossRefPubMed
2.
de Jonge S, van den Berg C, de Vos RJ, et al. Incidence of midportion Achilles tendinopathy in the general population. Br J Sports Med. 2011;45:1026–8.CrossRefPubMed
3.
Albers IS, Zwerver J, Diercks RL, et al. Incidence and prevalence of lower extremity tendinopathy in a Dutch general practice population: a cross sectional study. BMC Musculoskelet Disord. 2016;17:16.CrossRefPubMedPubMedCentral
4.
Khan KM, Cook JL, Bonar F, et al. Histopathology of common tendinopathies. Update and implications for clinical management. Sports Med. 1999;27:393–408.CrossRefPubMed
5.
Scott A, Backman L, Speed C. Tendinopathy-Update on Pathophysiology. J Orthop Sports Phys Ther. 2015;45:833–41.CrossRefPubMed
6.
Spang C, Harandi VM, Alfredson H, Forsgren S. Marked innervation but also signs of nerve degeneration in between the Achilles and plantaris tendons and presence of innervation within the plantaris tendon in midportion Achilles tendinopathy. J Musculoskelet Neuronal Interact. 2015;15:197–206.PubMedPubMedCentral
7.
Masci L, Spang C, van Schie HT, Alfredson H. How to diagnose plantaris tendon involvement in midportion Achilles tendinopathy - clinical and imaging findings. BMC Musculoskelet Disord. 2016;17:97.CrossRefPubMedPubMedCentral
8.
9.
Docking S, Samiric T, Scase E, et al. Relationship between compressive loading and ECM changes in tendons. Muscles Ligaments Tendons J. 2013;3:7–11.PubMedPubMedCentral
10.
Oliva F, Piccirilli E, Berardi AC, et al. Hormones and tendinopathies: the current evidence. Br Med Bull. 2016;117:39–58.CrossRefPubMed
11.
Danielson P. Reviving the “biochemical” hypothesis for tendinopathy: new findings suggest the involvement of locally produced signal substances. Br J Sports Med. 2009;43:265–8.CrossRefPubMed
12.
Skjong CC, Meininger AK, Ho SS. Tendinopathy treatment: where is the evidence? Clin Sports Med. 2012;31:329–50.CrossRefPubMed
13.
Buttgereit F, Spies CM, Bijlsma JW. Novel glucocorticoids: where are we now and where do we want to go? Clin Exp Rheumatol. 2015;33:S29–33.PubMed
14.
Maffulli N, Khan KM, Puddu G. Overuse tendon conditions: time to change a confusing terminology. Arthroscopy. 1998;14:840–3.CrossRefPubMed
15.
16.
Al-Sadi O, Schulze-Tanzil G, Kohl B, et al. Tenocytes, pro-inflammatory cytokines and leukocytes: a relationship? Muscles Ligaments Tendons J. 2012;1:68–76.PubMedPubMedCentral
17.
Rees JD, Stride M, Scott A. Tendons-time to revisit inflammation. Br J Sports Med. 2014;48:1553–7.CrossRefPubMed
18.
19.
Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet. 2010;376:1751–67.CrossRefPubMed
20.
21.
22.
23.
24.
Kotnis RA, Halstead JC, Hormbrey PJ. Atraumatic bilateral Achilles tendon rupture: an association of systemic steroid treatment. J Accid Emerg Med. 1999;16:378–9.CrossRefPubMedPubMedCentral
25.
Madsen BL, Noer HH. Simultaneous rupture of both peroneal tendons after corticosteroid injection: operative treatment. Injury. 1999;30:299–300.CrossRefPubMed
26.
Smith AG, Kosygan K, Williams H, Newman RJ. Common extensor tendon rupture following corticosteroid injection for lateral tendinosis of the elbow. Br J Sports Med. 1999;33:423–4.CrossRefPubMedPubMedCentral
27.
Mills SP, Charalambous CP, Hayton MJ. Bilateral rupture of the extensor pollicis longus tendon in a professional goalkeeper following steroid injections for extensor tenosynovitis. Hand Surg. 2009;14:135–7.CrossRefPubMed
28.
Zhang B, Hu ST, Zhang YZ. Spontaneous rupture of multiple extensor tendons following repeated steroid injections: a case report. Orthop Surg. 2012;4:118–21.CrossRefPubMed
29.
Dean BJ, Lostis E, Oakley T, et al. The risks and benefits of glucocorticoid treatment for tendinopathy: a systematic review of the effects of local glucocorticoid on tendon. Semin Arthritis Rheum. 2014;43:570–6.CrossRefPubMed
30.
Kempka G, Ahr HJ, Ruther W, Schluter G. Effects of fluoroquinolones and glucocorticoids on cultivated tendon cells in vitro. Toxicol In Vitro. 1996;10:743–54.CrossRefPubMed
31.
Tsai WC, Tang FT, Wong MK, et al. Decreased expression of proliferating cell nuclear antigen is associated with dexamethasone inhibition of the proliferation of rat tendon fibroblasts. J Rheumatol. 2002;29:2397–402.PubMed
32.
Wong MW, Tang YY, Lee SK, et al. Effect of dexamethasone on cultured human tenocytes and its reversibility by platelet-derived growth factor. J Bone Joint Surg Am. 2003;85-A:1914–20.CrossRefPubMed
33.
Wong MW, Tang YY, Lee SK, Fu BS. Glucocorticoids suppress proteoglycan production by human tenocytes. Acta Orthop. 2005;76:927–31.CrossRefPubMed
34.
Wong MW, Lui WT, Fu SC, Lee KM. The effect of glucocorticoids on tendon cell viability in human tendon explants. Acta Orthop. 2009;80:363–7.CrossRefPubMed
35.
Carofino B, Chowaniec DM, McCarthy MB, et al. Corticosteroids and local anesthetics decrease positive effects of platelet-rich plasma: an in vitro study on human tendon cells. Arthroscopy. 2012;28:711–9.CrossRefPubMed
36.
Olchowik G, Siek E, Tomaszewska M, Tomaszewski M. The evaluation of mechanical properties of animal tendons after corticosteroid therapy. Folia Histochem Cytobiol. 2008;46:373–7.CrossRefPubMed
37.
Hossain MA, Park J, Choi SH, Kim G. Dexamethasone induces apoptosis in proliferative canine tendon cells and chondrocytes. Vet Comp Orthop Traumatol. 2008;21:337–42.PubMed
38.
Sendzik J, Shakibaei M, Schafer-Korting M, et al. Synergistic effects of dexamethasone and quinolones on human-derived tendon cells. Int J Antimicrob Agents. 2010;35:366–74.CrossRefPubMed
39.
Young BB, Gordon MK, Birk DE. Expression of type XIV collagen in developing chicken tendons: association with assembly and growth of collagen fibrils. Dev Dyn. 2000;217:430–9.CrossRefPubMed
40.
Ansorge HL, Meng X, Zhang G, et al. Type XIV Collagen Regulates Fibrillogenesis: Premature collagen fibril growth and tissue dysfunction in null mice. J Biol Chem. 2009;284:8427–38.CrossRefPubMedPubMedCentral
41.
Zhang J, Keenan C, Wang JH. The effects of dexamethasone on human patellar tendon stem cells: implications for dexamethasone treatment of tendon injury. J Orthop Res. 2013;31:105–10.CrossRefPubMed
42.
Chen W, Tang H, Zhou M, et al. Dexamethasone inhibits the differentiation of rat tendon stem cells into tenocytes by targeting the scleraxis gene. J Steroid Biochem Mol Biol. 2015;152:16–24.CrossRefPubMed
43.
Chen W, Tang H, Liu X, et al. Dickkopf1 Up-Regulation Induced by a High Concentration of Dexamethasone Promotes Rat Tendon Stem Cells to Differentiate Into Adipocytes. Cell Physiol Biochem. 2015;37:1738–49.CrossRefPubMed
44.
Spang C, Alfredson H. Ferguson et al. The plantaris tendon in association with mid-portion Achilles tendinosis: tendinosis-like morphological features and presence of a non-neuronal cholinergic system. Histol Histopathol. 2013;28:623–32.PubMed
45.
Masci L, Spang C, van Schie HTM, et al. Achilles tendinopathy-do plantaris tendon removal and Achilles tendon scraping improve tendon structure? A prospective study using ultrasound tissue characterization. BMJ Open Sport Exerc Med. 2015;1:e000005.CrossRefPubMedPubMedCentral
46.
Backman LJ, Fong G, Andersson G, et al. Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation. PLoS One. 2011;6:e27209.CrossRefPubMedPubMedCentral
47.
Chen J, Zhang W, Liu Z, et al. Characterization and comparison of post-natal rat Achilles tendon-derived stem cells at different development stages. Sci Rep. 2016;6:22946.CrossRefPubMedPubMedCentral
48.
Liu H, Zhu S, Zhang C, et al. Crucial transcription factors in tendon development and differentiation: their potential for tendon regeneration. Cell Tissue Res. 2014;356:287–98.CrossRefPubMed
49.
50.
Poulsen RC, Watts AC, Murphy RJ, et al. Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53/p21 pathway: in vivo and in vitro evidence. Ann Rheum Dis. 2012;73:1405–13.CrossRef
51.
Galdiero M, Auriemma RS, Pivonello R, et al. Cushing, acromegaly, GH deficiency and tendons. Muscles Ligaments Tendons J. 2014;4:329–32.PubMedPubMedCentral
Metadata
Title
The tenocyte phenotype of human primary tendon cells in vitro is reduced by glucocorticoids
Authors
Christoph Spang
Jialin Chen
Ludvig J. Backman
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2016
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-016-1328-9

Other articles of this Issue 1/2016

BMC Musculoskeletal Disorders 1/2016 Go to the issue

Research article

Influence of ankle fracture surgery on glycemic control in patients with diabetes

Research article

Dual-energy computed tomography has limited sensitivity for non-tophaceous gout: a comparison study with tophaceous gout

Research article

Effectiveness of a telemonitoring intensive strategy in early rheumatoid arthritis: comparison with the conventional management approach

Research article

Low vitamin D and the risk of developing chronic widespread pain: results from the European male ageing study

Research article

Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen-induced arthritis rats

Research article

Physical therapists’ assessments, analyses and use of behavior change techniques in initial consultations on musculoskeletal pain: direct observations in primary health care