Sage Journals: Discover world-class research

Abstract

Background

Treatment of midportion Achilles tendinopathy is hampered by limited knowledge of the pathophysiology.

Hypothesis

Chondrogenic differentiation of tendon cells might take place in midportion Achilles tendinopathy and could be used as a target for drug treatment. An in vitro model for chondrogenic differentiation would be useful to evaluate existing and future treatment opportunities.

Study Design

Descriptive and controlled laboratory study.

Methods

Perioperatively harvested tissue from human midportion Achilles tendinotic lesions and healthy Achilles tendons was analyzed by microscopy and real-time reverse transcription polymerase chain reaction. In vitro chondrogenic differentiation of tendon explants was induced using transforming-growth-factor beta. This model was modulated by removing the chondrogenic stimulus or adding triamcinolone or platelet-rich plasma.

Results

Midportion Achilles tendinotic lesions had increased glycosaminoglycan staining and more rounded cell nuclei. Chondrogenic markers (sex-determining region Y)–box9, aggrecan, collagen 2, and RUNT-related transcription factor 2 were upregulated, but collagen 10 was not. Nondegenerative tendon explants cultured on chondrogenic medium had higher expression of aggrecan, collagen 2, and collagen 10 but not (sex-determining region Y)–box9 and RUNT-related transcription factor 2. Removing the chondrogenic stimulus decreased expression of aggrecan, collagen 2, and collagen 10. Both triamcinolone and platelet-rich plasma influenced the chondrogenic gene expression pattern in the in vitro model.

Conclusion

Chondrogenic differentiation is present in midportion Achilles tendinopathy. An in vitro model to study this chondrogenic differentiation was developed.

Clinical Relevance

This model can be used to investigate chondrogenic differentiation as a possible target for drug treatment, contributing to the development of more successful mechanism-based treatment opportunities.

Keywords

Achilles tendinopathy chondrogenic differentiation in vitro model platelet-rich plasma (PRP)triamcinolone

Get full access to this article

View all access options for this article.

References

Almekinders

Weinhold

Maffulli

. Compression etiology in tendinopathy. Clin Sports Med. 2003;22:703–710.

Archambault

Jelinsky

Lake

Hill

Glaser

Soslowsky

. Rat supraspinatus tendon expresses cartilage markers with overuse. J Orthop Res. 2007;25:617–624.

Arndt

Komi

Bruggemann

Lukkariniemi

. Individual muscle contributions to the in vivo Achilles tendon force. Clin Biomech (Bristol, Avon). 1998;13:532–541.

Arnoczky

Lavagnino

Egerbacher

. The mechanobiological aetiopathogenesis of tendinopathy: is it the over-stimulation or the under-stimulation of tendon cells? . Int J Exp Pathol. 2007;88:217–226.

Arnoczky

Lavagnino

Egerbacher

Caballero

Gardner

. Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med. 2007;35:763–769.

Astrom

Rausing

. Chronic Achilles tendinopathy: a survey of surgical and histopathologic findings. Clin Orthop Relat Res. 1995;316:151–164.

Benjamin

Ralphs

. Fibrocartilage in tendons and ligaments: an adaptation to compressive load. J Anat. 1998;193(pt 4):481–494.

Caterson

Nesti

Danielson

Tuan

. Human marrow-derived mesenchymal progenitor cells: isolation, culture expansion, and analysis of differentiation. Mol Biotechnol. 2002;20:245–256.

Celotti

Colciago

Negri-Cesi

Pravettoni

Zaninetti

Sacchi

. Effect of platelet-rich plasma on migration and proliferation of SaOS-2 osteoblasts: role of platelet-derived growth factor and transforming growth factor-beta. Wound Repair Regen. 2006;14:195–202.

10.

Clement

Taunton

Smart

. Achilles tendinitis and peritendinitis: etiology and treatment. Am J Sports Med. 1984;12:179–184.

11.

Corps

Robinson

Movin

Costa

Hazleman

Riley

. Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy. Rheumatology (Oxford). 2006;45:291–294.

12.

de Mos

Koevoet

Jahr

. Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study. BMC Musculoskelet Disord. 2007;23:8–16.

13.

de Mos

van der Windt

Jahr

. Can platelet-rich plasma enhance tendon repair? A cell culture study. Am J Sports Med. 2008;36:1171–1178.

14.

de Mos

van El

Degroot

. Achilles tendinosis: changes in biochemical composition and collagen turnover rate. Am J Sports Med. 2007;35:1549–1556.

15.

Derfoul

Perkins

Hall

Tuan

. Glucocorticoids promote chondrogenic differentiation of adult human mesenchymal stem cells by enhancing expression of cartilage extracellular matrix genes. Stem Cells. 2006;24:1487–1495.

16.

Fenwick

Curry

Harrall

Hazleman

Hackney

Riley

. Expression of transforming growth factor–beta isoforms and their receptors in chronic tendinosis. J Anat. 2001;199:231–240.

17.

Wang

Pau

Wong

Chan

Rolf

. Increased expression of transforming growth factor–beta1 in patellar tendinosis. Clin Orthop Relat Res. 2002;400:174–183.

18.

Grigoriadis

Aubin

Heersche

. Effects of dexamethasone and vitamin D3 on cartilage differentiation in a clonal chondrogenic cell population. Endocrinology. 1989;125:2103–2110.

19.

Gruber

Karreth

Kandler

. Platelet-released supernatants increase migration and proliferation, and decrease osteogenic differentiation of bone marrow–derived mesenchymal progenitor cells under in vitro conditions. Platelets. 2004;15:29–35.

20.

Heinemeier

Langberg

Kjaer

. Exercise-induced changes in circulating levels of transforming growth factor–beta-1 in humans: methodological considerations. Eur J Appl Physiol. 2003;90:171–177.

21.

Livak

Schmittgen

. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–408.

22.

Maffulli

Kader

. Tendinopathy of tendo achillis. J Bone Joint Surg Br. 2002;84:1–8.

23.

Maffulli

Reaper

Ewen

Waterston

Barrass

. Chondral metaplasia in calcific insertional tendinopathy of the Achilles tendon. Clin J Sport Med. 2006;16:329–334.

24.

Mishra

Pavelko

. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med. 2006;34:1774–1778.

25.

Movin

Gad

Reinholt

Rolf

. Tendon pathology in longstanding achillodynia: biopsy findings in 40 patients. Acta Orthop Scand. 1997;68:170–175.

26.

O’Brien

. Functional anatomy and physiology of tendons. Clin Sports Med. 1992;11:505–520.

27.

Ohno

Tanaka

Ueki

. Mechanical regulation of terminal chondrocyte differentiation via RGD-CAP/beta ig-h3 induced by TGF-beta. Connect Tissue Res. 2005;46:227–234.

28.

Pauwels

. A new theory on the influence of mechanical stimuli on the differentiation of supporting tissue: the tenth contribution to the functional anatomy and causal morphology of the supporting structure [in German]. Z Anat Entwicklungsgesch. 1960;121:478–515.

29.

Pufe

Petersen

Mentlein

Tillmann

. The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease. Scand J Med Sci Sports. 2005;15:211–222.

30.

Riley

. The pathogenesis of tendinopathy: a molecular perspective. Rheumatology (Oxford). 2004;43:131–142.

31.

Salingcarnboriboon

Yoshitake

Tsuji

. Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property. Exp Cell Res. 2003;287:289–300.

32.

Schnabel

Mohammed

Miller

. Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons. J Orthop Res. 2007;25:230–240.

33.

See

. Intra-synovial corticosteroid injections in juvenile chronic arthritis: a review. Ann Acad Med Singapore. 1998;27:105–111.

34.

Smith

Birch

Goodman

Heinegard

Goodship

. The influence of ageing and exercise on tendon growth and degeneration: hypotheses for the initiation and prevention of strain-induced tendinopathies. Comp Biochem Physiol A Mol Integr Physiol. 2002;133:1039–1050.

35.

Tallon

Maffulli

Ewen

. Ruptured Achilles tendons are significantly more degenerated than tendinopathic tendons. Med Sci Sports Exerc. 2001;33:1983–1990.

36.

Tanaka

Murphy

Kimura

Kawai

Polak

. Chondrogenic differentiation of murine embryonic stem cells: effects of culture conditions and dexamethasone. J Cell Biochem. 2004;93:454–462.

37.

Terraciano

Hwang

Moroni

. Differential response of adult and embryonic mesenchymal progenitor cells to mechanical compression in hydrogels. Stem Cells. 2007;25:2730–2738.

38.

van den Dolder

Mooren

Vloon

Stoelinga

Jansen

. Platelet-rich plasma: quantification of growth factor levels and the effect on growth and differentiation of rat bone marrow cells. Tissue Eng. 2006;12:3067–3073.

39.

Wang

Iosifidis

. Biomechanical basis for tendinopathy. Clin Orthop Relat Res. 2006;443:320–332.

40.

Weiss

Livne

Silbermann

. Glucocorticoid hormone adversely affects the growth and regeneration of cartilage in vitro. Growth Dev Aging. 1988;52:67–75.

41.

Wilson

Goodship

. Exercise-induced hyperthermia as a possible mechanism for tendon degeneration. J Biomech. 1994;27:899–905.

42.

Wilson

Best

. Common overuse tendon problems: a review and recommendations for treatment. Am Fam Physician. 2005;72:811–818.

In Vitro Model to Study Chondrogenic Differentiation in Tendinopathy

Abstract

Background

Hypothesis

Study Design

Methods

Results

Conclusion

Clinical Relevance

Keywords

Get full access to this article

References