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 1/2013

Open Access 01-12-2013 | Research article

Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes

Authors: Tung-Yang Yu, Jong-Hwei S Pang, Katie Pei-Hsuan Wu, Max J-L Chen, Chien-Hung Chen, Wen-Chung Tsai

Published in: BMC Musculoskeletal Disorders | Issue 1/2013

Login to get access

Abstract

Background

Most tendon pathology is associated with degeneration, which is thought to involve cyclic loading and cumulative age-related changes in tissue architecture. However, the association between aging and degeneration of the extracellular matrix (ECM) in tendons has not been investigated extensively.

Methods

We examined tenocytes from Achilles tendons taken from rats of three different ages (2, 12, and 24 months). Tenocyte viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative real-time polymerase chain reaction (PCR) was used to determine the levels of mRNAs that encode type-I collagen, matrix metalloproteinase (MMP)-2 and −9, tissue inhibitor of metalloproteinase (TIMP)-1 and −2 and transforming growth factor (TGF)-β1. Gelatin zymography was used to evaluate the enzymatic activities of MMP-2 and −9. Furthermore, the concentration of TGF-β1 in conditioned medium was evaluated using enzyme-linked immunosorbent assay (ELISA).

Results

The results of the MTT assay showed that the number of viable tenocytes decreased with age. No differences were observed in the levels of mRNAs that encode type-I collagen and TGF-β1 among the three age groups, and the TGF-β1 concentration did not change with age. However, mRNAs that encode MMP-2 and −9 were significantly more abundant in tenocytes from the aging group, and gelatin zymography revealed that the enzymatic activities of MMP-2 and −9 also increased significantly with age. Furthermore, as compared with young group, mRNAs that encode TIMP-1 and −2 were significantly decreased in tenocytes from the aging group.

Conclusions

Activities of MMP-2 and MMP-9 in tenocytes increase with age. This might provide a mechanistic explanation of how aging contributes to tendinopathy or tendon rupture with age.
Appendix
Available only for authorised users
Literature
1.
Chard MD, Cawston TE, Riley GP, Gresham GA, Hazleman BL: Rotator cuff degeneration and lateral epicondylitis: a comparative histological study. Ann Rheum Dis. 1994, 53: 30-34. 10.1136/ard.53.1.30.CrossRefPubMedPubMedCentral
2.
Astrom M, Rausing A: Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings. Clin Orthop Relat Res. 1995, 316: 151-164.PubMed
3.
Dressler MR, Butler DL, Wenstrup R, Awad HA, Smith F, Boivin GP: A potential mechanism for age-related declines in patellar tendon biomechanics. J Orthop Res. 2002, 20: 1315-1322. 10.1016/S0736-0266(02)00052-9.CrossRefPubMed
4.
Kannus P, Jozsa L: Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am. 1991, 73: 1507-1525.PubMed
5.
Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP: Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum. 2006, 54: 832-842. 10.1002/art.21672.CrossRefPubMed
6.
Riley G: The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford). 2004, 43: 131-142.CrossRef
7.
Riley G: Tendinopathy–from basic science to treatment. Nat Clin Pract Rheumatol. 2008, 4: 82-89. 10.1038/ncprheum0700.CrossRefPubMed
8.
Riley GP, Curry V, DeGroot J, van El B, Verzijl N, Hazleman BL, Bank RA: Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol. 2002, 21: 185-195. 10.1016/S0945-053X(01)00196-2.CrossRefPubMed
9.
Visse R, Nagase H: Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003, 92: 827-839. 10.1161/01.RES.0000070112.80711.3D.CrossRefPubMed
10.
Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G: Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol. 2001, 20: 159-169. 10.1016/S0945-053X(01)00128-7.CrossRefPubMed
11.
Salo T, Turpeenniemi-Hujanen T, Tryggvason K: Tumor-promoting phorbol esters and cell proliferation stimulate secretion of basement membrane (type IV) collagen-degrading metalloproteinase by human fibroblasts. J Biol Chem. 1985, 260: 8526-8531.PubMed
12.
Aimes RT, Quigley JP: Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J Biol Chem. 1995, 270: 5872-5876. 10.1074/jbc.270.11.5872.CrossRefPubMed
13.
Dudhia J, Scott CM, Draper ER, Heinegard D, Pitsillides AA, Smith RK: Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell. 2007, 6: 547-556. 10.1111/j.1474-9726.2007.00307.x.CrossRefPubMed
14.
Kingsley DM: The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 1994, 8: 133-146. 10.1101/gad.8.2.133.CrossRefPubMed
15.
Molloy T, Wang Y, Murrell G: The roles of growth factors in tendon and ligament healing. Sports Med. 2003, 33: 381-394. 10.2165/00007256-200333050-00004.CrossRefPubMed
16.
Sporn MB, Roberts AB, Shull JH, Smith JM, Ward JM, Sodek J: Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science. 1983, 219: 1329-1331. 10.1126/science.6572416.CrossRefPubMed
17.
Wrana JL, Sodek J, Ber RL, Bellows CG: The effects of platelet-derived transforming growth factor beta on normal human diploid gingival fibroblasts. Eur J Biochem. 1986, 159: 69-76. 10.1111/j.1432-1033.1986.tb09834.x.CrossRefPubMed
18.
Kerr LD, Miller DB, Matrisian LM: TGF-beta 1 inhibition of transin/stromelysin gene expression is mediated through a Fos binding sequence. Cell. 1990, 61: 267-278. 10.1016/0092-8674(90)90807-Q.CrossRefPubMed
19.
Kerr LD, Olashaw NE, Matrisian LM: Transforming growth factor beta 1 and cAMP inhibit transcription of epidermal growth factor- and oncogene-induced transin RNA. J Biol Chem. 1988, 263: 16999-17005.PubMed
20.
Overall CM, Wrana JL, Sodek J: Independent regulation of collagenase, 72-kDa progelatinase, and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-beta. J Biol Chem. 1989, 264: 1860-1869.PubMed
21.
Overall CM, Wrana JL, Sodek J: Transforming growth factor-beta regulation of collagenase, 72 kDa-progelatinase, TIMP and PAI-1 expression in rat bone cell populations and human fibroblasts. Connect Tissue Res. 1989, 20: 289-294. 10.3109/03008208909023899.CrossRefPubMed
22.
Deie M, Marui T, Allen CR, Hildebrand KA, Georgescu HI, Niyibizi C, Woo SL: The effects of age on rabbit MCL fibroblast matrix synthesis in response to TGF-beta 1 or EGF. Mech Ageing Dev. 1997, 97: 121-130. 10.1016/S0047-6374(97)00049-3.CrossRefPubMed
23.
Tsai WC, Pang JH, Hsu CC, Chu NK, Lin MS, Hu CF: Ultrasound stimulation of types I and III collagen expression of tendon cell and upregulation of transforming growth factor beta. J Orthop Res. 2006, 24: 1310-1316. 10.1002/jor.20130.CrossRefPubMed
24.
Leadbetter WB: Cell-matrix response in tendon injury. Clin Sports Med. 1992, 11: 533-578.PubMed
25.
Broughton G, Janis JE, Attinger CE: Wound healing: an overview. Plast Reconstr Surg. 2006, 117: 1e-S-32e-S.CrossRef
26.
Van de Kerkhof PC, Van Bergen B, Spruijt K, Kuiper JP: Age-related changes in wound healing. Clin Exp Dermatol. 1994, 19: 369-374. 10.1111/j.1365-2230.1994.tb02684.x.CrossRefPubMed
27.
Bruce SA, Deamond SF: Longitudinal study of in vivo wound repair and in vitro cellular senescence of dermal fibroblasts. Exp Gerontol. 1991, 26: 17-27. 10.1016/0531-5565(91)90058-T.CrossRefPubMed
28.
Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL: Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis. 1994, 53: 359-366. 10.1136/ard.53.6.359.CrossRefPubMedPubMedCentral
29.
Sharma P, Maffulli N: Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact. 2006, 6: 181-190.PubMed
30.
Lindsey ML, Goshorn DK, Squires CE, Escobar GP, Hendrick JW, Mingoia JT, Sweterlitsch SE, Spinale FG: Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function. Cardiovasc Res. 2005, 66: 410-419. 10.1016/j.cardiores.2004.11.029.CrossRefPubMed
31.
Mine S, Fortunel NO, Pageon H, Asselineau D: Aging alters functionally human dermal papillary fibroblasts but not reticular fibroblasts: a new view of skin morphogenesis and aging. PLoS One. 2008, 3: e4066-10.1371/journal.pone.0004066.CrossRefPubMedPubMedCentral
32.
Gepstein A, Shapiro S, Arbel G, Lahat N, Livne E: Expression of matrix metalloproteinases in articular cartilage of temporomandibular and knee joints of mice during growth, maturation, and aging. Arthritis Rheum. 2002, 46: 3240-3250. 10.1002/art.10690.CrossRefPubMed
33.
Bonnema DD, Webb CS, Pennington WR, Stroud RE, Leonardi AE, Clark LL, McClure CD, Finklea L, Spinale FG, Zile MR: Effects of age on plasma matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). J Card Fail. 2007, 13: 530-540. 10.1016/j.cardfail.2007.04.010.CrossRefPubMedPubMedCentral
34.
Chan KM, Fu SC, Wong YP, Hui WC, Cheuk YC, Wong MW: Expression of transforming growth factor beta isoforms and their roles in tendon healing. Wound Repair Regen. 2008, 16: 399-407. 10.1111/j.1524-475X.2008.00379.x.CrossRefPubMed
35.
Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty AJ, Angel P, Heath JK: Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J. 1987, 6: 1899-1904.PubMedPubMedCentral
36.
Robbins JR, Evanko SP, Vogel KG: Mechanical loading and TGF-beta regulate proteoglycan synthesis in tendon. Arch Biochem Biophys. 1997, 342: 203-211. 10.1006/abbi.1997.0102.CrossRefPubMed
37.
Fu SC, Wang W, Pau HM, Wong YP, Chan KM, Rolf CG: Increased expression of transforming growth factor-beta1 in patellar tendinosis. Clin Orthop Relat Res. 2002, 400: 174-183.CrossRefPubMed
38.
Fu SC, Cheuk YC, Chan KM, Hung LK, Wong MW: Is cultured tendon fibroblast a good model to study tendon healing?. J Orthop Res. 2008, 26: 374-383. 10.1002/jor.20483.CrossRefPubMed
39.
Leigh DR, Abreu EL, Derwin KA: Changes in gene expression of individual matrix metalloproteinases differ in response to mechanical unloading of tendon fascicles in explant culture. J Orthop Res. 2008, 26: 1306-1312. 10.1002/jor.20650.CrossRefPubMed
40.
Sprenger CC, Plymate SR, Reed MJ: Aging-related alterations in the extracellular matrix modulate the microenvironment and influence tumor progression. Int J Cancer. 2010, 127: 2739-2748. 10.1002/ijc.25615.CrossRefPubMedPubMedCentral
41.
Pradel W, Mai R, Gedrange T, Lauer G: Cell passage and composition of culture medium effects proliferation and differentiation of human osteoblast-like cells from facial bone. J Physiol Pharmacol. 2008, 59 (Suppl 5): 47-58.PubMed
42.
Sun YL, Thoreson AR, Cha SS, Zhao C, An KN, Amadio PC: Temporal response of canine flexor tendon to limb suspension. J Appl Physiol. 2010, 109: 1762-1768. 10.1152/japplphysiol.00051.2010.CrossRefPubMedPubMedCentral
43.
Kjaer M: Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev. 2004, 84: 649-698. 10.1152/physrev.00031.2003.CrossRefPubMed
Metadata
Title
Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes
Authors
Tung-Yang Yu
Jong-Hwei S Pang
Katie Pei-Hsuan Wu
Max J-L Chen
Chien-Hung Chen
Wen-Chung Tsai
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2013
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-14-2

Other articles of this Issue 1/2013

BMC Musculoskeletal Disorders 1/2013 Go to the issue

Research article

Association of back pain with hypovitaminosis D in postmenopausal women with low bone mass

Research article

Do orthopaedic shoes improve local dynamic stability of gait? An observational study in patients with chronic foot and ankle injuries

Research article

2D-fluoroscopic based navigation for Gamma 3 nail insertion versus conventional procedure- a feasibility study

Study protocol

Strength Training for Arthritis Trial (START): design and rationale

Research article

At the moment of occurrence of a fragility hip fracture, men have higher mechanical properties values in comparison with women

Research article

Myofascial trigger points and innervation zone locations in upper trapezius muscles