trends in matrix metalloproteinase research from 1986–2007: a bibliometric study

Trends in matrix metalloproteinase research from1986–2007: a bibliometric study

Claude Robert, Concepcion S. Wilson, Jean-Francois Gaudy, William Hornebeck,and Charles-Daniel Arreto

Abstract: Using the SCI-expanded database, this study provides a quantitative description of the development of the re-search involving matrix metalloproteinase (MMP) over a period of 20 years. From 1986 to 2007 the scientific literature re-lated to MMP increased sevenfold (397 papers in 1986–1987 and 2834 in 2006–2007). The number of countriesparticipating in MMP-related research doubled during this period (33 in 1986–1987 to 67 in 2006–2007), and the USAcontinually remained the leader. Several industrialized nations (Japan, Germany, UK, Canada, and France) also continu-ously played important roles, with some emerging Asian countries joining the top 10 most productive countries in 2006–2007: China (ranked 5th), South Korea (6th), and Taiwan (10th). The MMP-related literature was distributed among a con-tinuously growing number of journals (188 in 1986–1987, 527 in 1996–1997, and 913 in 2006–2007) and The Journal ofBiological Chemistry remained the most prolific throughout the entire period. The development of the research involvingMMPs during the past two decades was also characterized by a progressive transfer of interest from basic research to clini-cal medicine; cell biology and pharmacology were important routes of investigation generally pursued by researchers. Jour-nals dedicated to oncology have progressively risen to the top 8 most prolific journals during the 20 year period analyzed.

Key words: matrix metalloproteinase, MMP, journal analysis, cancer research, bibliometrics.

Resume : Menee sur la base de donnees SCI-expanded, cette etude presente une description quantitative du developpe-ment de la recherche sur les metalloproteases matricielles sur une periode de 20 ans. De 1986 a 2007, la litterature scienti-fique en lien avec les MMP s’est accrue d’un facteur 7 (397 articles en 1986–1987 a 2834 en 2006–2007). Durant laperiode 1986–2007, le nombre de pays participant a la recherche sur les MMP a double (33 en 1986–1987 et 67 en 2006–2007), et les Etats-Unis ont maintenu leur position de leader. Plusieurs pays industrialises (Japon, Allemagne, Royaume-Uni, Canada et France) ont aussi joue un role important, avec quelques pays emergents d’Asie qui se sont joint aux dixpays les plus productifs en 2006–2007 : la Chine (5ieme rang), la Coree du Sud (6ieme) et Taiwan (10ieme). La litterature re-liee aux MMP etait distribuee a travers un nombre croissant de revues scientifiques (188 en 1986–1987, 527 en 1996–1997 et 913 en 2006–2007), et The Journal of Biological Chemistry est demeuree la plus prolifique durant toute cette pe-riode. Le developpement de la recherche sur les MMP au cours des deux dernieres decennies a aussi ete caracterise par untransfert progressif de l’interet de la recherche fondamentale vers la medecine clinique ; la biologie cellulaire et la pharma-cologie ont constitue des voies de recherche importantes generalement poursuivies par les chercheurs. Au cours de la pe-riode analysee, des revues specialisees dans la recherche en oncologie ont progressivement integre le top-8 des revues lesplus prolifiques.

Mots-cles : metalloproteases matricielles, MMP, analyse des revues scientifiques, recherche sur le cancer, bibliometrie.

[Traduit par la Redaction]

IntroductionAmong the various types of proteinases involved in ex-

tracellular matrix degradation, a predominant group is thematrix metalloproteinases (MMPs) or matrixins. MMPswere described in a seminal study in which fragments of re-sorbing tadpole tail were able to dissolve a network of colla-gen fibrils leading to the formation of an opalescentcollagen gel (Gross and Lapiere 1962). Further studies deter-

mined the nature of the collagenolytic activity (Gross andNagai 1965; Sakai and Gross 1967). A decade later, the tis-sue inhibitors of metalloproteinases (TIMPs) were discov-ered (Bauer et al. 1975), and the implication of MMPs in agreat many processes concerning either normal developmentand growth or pathological processes (arthritis, cancer tu-morigenesis) were observed. With time, the field of MMPresearch grew along with its scientific literature output

Received 5 October 2009. Revision received 10 January 2010. Accepted 19 January 2010. Published on the NRC Research Press Website at bcb.nrc.ca on 28 September 2010.

C. Robert,1 J.-F. Gaudy, and C.-D. Arreto. Universite Paris Descartes, Faculte de Chirurgie Dentaire, Laboratoire d’AnatomieFonctionnelle, 1 rue Maurice Arnoux, 92 120 Montrouge, France.C.S. Wilson. School of Information Systems, Technology and Management, The University of New South Wales, Sydney, Australia.W. Hornebeck. Universite de Reims Champagne-Ardenne, ICMR-UMR 6229 CNRS, Faculte de Pharmacie, 51 rue Cognacq Jay, 51095Reims, France.

1Corresponding author (e-mail: [email protected]).

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Biochem. Cell Biol. 88: 843–851 (2010) doi:10.1139/O10-006 Published by NRC Research Press

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(Fig. 1); there are now at least 25 distinct vertebrate MMPsrecognized.

As for all fields of science, numerous reviews refer to theimportant advances of MMPs in various experimental andclinical domains (Egeblad and Werb 2002; Burrage andBrinckerhof 2007; Krane and Inada 2008; Scherer et al.2008) and illustrate the dramatic increase of scientific do-mains involving MMPs. In these review papers, the historicalevolution of MMP research is generally only briefly described(Murphy and Nagase 2008), with Woessner (2002) providing adetailed historical perspective on MMPs and TIMPs. In con-trast, there are few quantitative descriptions of the MMP litera-ture, with one recently published by Lapiere (2005), in whichhe used data provided by Woessner, as well as the PubMed da-tabase, to chart the evolution of the number of publications peryear since the 1962 seminal paper to ~2001 in approximately10 year growth phases: early life (1962–1971), adolescence(1972–1981), the progressing phase (1982–1991), and the ex-panding phase from 1992 onwards, with a total of more than25 000 publications up to the end of 2003.

This paper provides the reader with a quantitative descrip-tion of the evolution of research involving MMPs from1986–2007, i.e., overlapping with the progressing and ex-panding phases of Lapiere (2005) but from a broader per-spective of scientific research using the Web of Sciencedatabases. Results are presented and discussed in terms ofthe productivity of researchers based on their affiliatedcountries or regions and the distribution of journals publish-ing the research, including their impact factors (IFs): the IFsof the journals provide a measure of quality and subsequentinfluence on researchers as authors, while the subject cate-gories of journals designate the various scientific subfieldswhere MMP research papers are published.

MethodsThe raw data for this study were obtained in May 2009

from the SCI-expanded database of Thomson ScientificWeb of ScienceTM. To retrieve a comprehensive set ofMMP-related literature, all documents published in journalswith at least one of the following keywords in the titleswere included: endopeptidase*, matrilysin*, collagenase*,stromelysin*, matrixin*, gelatinase*, RASI-1, enamelysin*,epilysin*, metallopeptidase, metalloproteinase*, metallopro-tein*, transin*, proteoglycanase*, leukolysin*, endometase*,metalloelastase*, PUMP-1, macrophage elastase*, MMP*,metalloprotease*, ADAM protein, serralysin*, astacin*,ADAM-, ADAM1*, ADAM2*, ADAM3*, ADAM4*,ADAM5*, ADAM6*, ADAM7*, ADAM8*, ADAM9*,ADAM0*, ADAMT*, or RECK*, where an asterisk replacesany subsequent string of characters. The search was re-stricted to include only articles and reviews. The search key-word TIMP* was not used, as it was thought that papersdealing with TIMPs (tissue inhibitors of metalloproteinases)would have referred to the full name and that the set of key-words used (e.g., metalloproteinase*) was sufficient.

For each time period (1986–1987, 1996–1997, and 2006–2007), data sets were manipulated using Microsoft Excel,analyzed, and ranked in decreasing order of productivity bycountry, language, journal, and subject area. Multi-authoredpublications were assigned equally to each country appear-

ing in the author address field and publications from Eng-land, Wales, Scotland, and Northern Ireland were assignedto the United Kingdom.

Results

Evolution of the MMP literatureThe evolution of the MMP-related literature shows an

overall growth from 1986 to 2007 of more than sevenfold(7.1) from 397 papers in 1986–1987 to 2833 in 2006–2007,while overall growth of all scientific literature was less thantwofold (1.7) from 1 427 620 papers in 1986–1977 to2 490 798 papers in 2006–2007 (Fig. 1).

The number of MMP publications retrieved and analyzedin each time period was 397 in 1986–1987, 1518 in 1996–1997, and 2833 in 2006–2007. During 1986–2007, the per-centage of review-type papers dramatically increased (from0.5% in 1986–1987 to 5.2% in 2006–2007), and the percent-age of English language papers grew from 93.9% in 1986–1987 to 99.6% in 2006–2007. Figure 1 shows a slight de-crease in the growth of the MMP literature in the last 2 years(2006–2007) as compared with the slight increase in the to-tal number of scientific papers in the same period.

Evolution of countries publishing MMP-related researchThe country share of the top 40 countries publishing

MMP-related research in 1986–1987, 1996–1997, and2006–2007 is displayed in Table 1, where countries areranked in decreasing order according to the number of pub-lications for each time period. Over all 3 periods, the num-ber of countries publishing doubled: 33 countries in 1986–1987, 44 in 1996–1997, and 67 in 2006–2007. In each timeperiod, the USA had the highest number of publications;however, its share has been declining from nearly one halfin 1986–1987 to less than one third in 2006–2007. In thefirst period (1986–1987) the top 10 most productive coun-tries were industrialized; however, by the last period (2006–2007), three Asian newcomers had appeared: China (5th),South Korea (6th), and Taiwan (10th). It is worth noting

Fig. 1. Time course of the scientific literature on MMPs during theperiod 1986–2007. For comparison of the MMP-related literature tothe overall scientific literature, data were normalized and expressedas a productivity index corresponding to the number of papers pub-lished during each 2 year period divided by the number of paperspublished during the first 2 year period (1986–1987).

844 Biochem. Cell Biol. Vol. 88, 2010

Published by NRC Research Press

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Table 1. Top 40 most productive countries publishing MMP-related papers in 1986–1987, 1996–1997, and 2006–2007.

1986–1987 1996–1997 2006–2007

Country/territoryNo. ofpapers

% (of397) Rank Country/territory

No. ofpapers

% (of1518) Rank Country/territory

No. ofpapers

% (of2833) Rank

USA 185 46.60 1 USA 654 43.08 1 USA 914 32.25 1UK 46 11.59 2 Japan 293 19.30 2 Japan 383 13.51 2Japan 38 9.57 3 UK 193 12.71 3 Germany* 227 8.01 3France 37 9.32 4 France 111 7.31 4 UK 222 7.83 4Germany* 25 6.30 5 Germany* 109 7.18 5 Peoples R China 202 7.13 5Canada 23 5.80 6 Canada 78 5.14 6 South Korea 172 6.07 6Switzerland 10 2.52 7 Italy 47 3.10 7 Canada 157 5.54 7Netherlands 9 2.27 8 Finland 44 2.90 8 France 134 4.73 8Poland 6 1.51 9 Belgium 39 2.57 9 Italy 129 4.55 9Finland 5 1.26 10 Spain 28 1.84 10 Taiwan 89 3.14 10Australia 5 1.26 10 Australia 28 1.84 10 Finland 77 2.72 11Russia 5 1.26 10 Netherlands 27 1.78 12 Spain 77 2.72 11Italy 4 1.01 13 Switzerland 18 1.19 13 Belgium 70 2.47 13Belgium 4 1.01 13 Sweden 17 1.12 14 Australia 68 2.40 14Sweden 4 1.01 13 South Korea 15 0.99 15 Brazil 65 2.29 15Brazil 3 0.76 16 Brazil 13 0.86 16 Netherlands 62 2.19 16Denmark 3 0.76 16 Israel 12 0.79 17 Sweden 53 1.87 17Israel 3 0.76 16 Denmark 10 0.66 18 Poland 49 1.73 18Norway 3 0.76 16 Ireland 9 0.59 19 India 46 1.62 19Czechoslovakia 3 0.76 16 Russia 9 0.59 19 Switzerland 45 1.59 20India 2 0.50 21 New Zealand 8 0.53 21 Denmark 42 1.48 21Mexico 2 0.50 21 Taiwan 7 0.46 22 Greece 30 1.06 22Hungary 2 0.50 26 Mexico 7 0.46 22 Israel 30 1.06 22South Africa 2 0.50 21 Norway 7 0.46 22 Turkey 29 1.02 24Ger. Dem. Rep. 2 0.50 21 Poland 6 0.40 25 Austria 21 0.74 25Peoples R China 1 0.25 26 Peoples R China 5 0.33 26 Ireland 21 0.74 25South Korea 1 0.25 26 India 3 0.20 28 Russia 21 0.74 25Costa Rica 1 0.25 26 Greece 3 0.20 28 Mexico 15 0.53 28Venezuela 1 0.25 26 Austria 3 0.20 28 Norway 13 0.46 29Afars and Issas 1 0.25 26 South Africa 3 0.20 28 Czech Republic 12 0.42 30Ivory Coast 1 0.25 26 Czech Republic 2 0.13 32 Thailand 11 0.39 31Kenya 1 0.25 26 Singapore 2 0.13 32 Singapore 10 0.35 32Yugoslavia 1 0.25 26 Argentina 2 0.13 32 Argentina 7 0.25 33

Romania 2 0.13 32 Hungary 7 0.25 33Bulgaria 2 0.13 32 Iran 7 0.25 33Lithuania 2 0.13 32 Portugal 6 0.21 36Moldova 2 0.13 32 Tunisia 6 0.21 36Romania 2 0.13 32 Romania 5 0.18 38Singapore 2 0.13 32 Saudi Arabia 5 0.18 38Croatia, Luxembourg,

Slovakia, Uruguay,Vietnam

1 0.07 40 Serbia 5 0.18 38

*For 1986–1987, the country is referred to as the Federal Republic of Germany.

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that in the 2006–2007 ranking, 23 of the 27 EuropeanUnion2 (EU) countries contributed to the MMP body of liter-ature; the 4 non-publishing EU countries were Cyprus, Esto-nia, Latvia, and Malta. Of the 23 publishing EU countries, 10were ranked in the top 20 most productive countries in 2007.

When the 2833 papers of the top 7 countries for the2006–2007 time period were analyzed vis-a-vis country-to-country collaboration, the USA was the preferred collabora-tive country from a high of 20.4% of Canadian papers (32 of157 papers) to 12.9% of 202 papers by Chinese MMP re-searchers. However, the USA’s preferred country for collab-oration (Japan) was only for 6.6% of its 914 papers (seeTable 2). The range in the number of collaborative countriesfor each of the top 7 nations was from a high of 38 for theUSA to a low of only 7 for South Korea.

Evolution of MMP-related papers in scientific subjectareas

The scientific literature on MMPs published during 1986–2007 covered a broad range of scientific subject areas: 70for 1986–1987, 100 for 1996–1997, and 110 for 2006–2007.The top 10 subject areas for each of the 3 time periods arepresented in Table 3; Biochemistry and molecular biologyranked first with 40% of the scientific papers in 1986–1987and approximately 20% in 2006–2007. Though some subjectareas were present in all 3 periods (Biochemistry and molec-ular biology, Cell biology, and Pharmacology and phar-macy), others emerged in either the 1996–1997 time period(Oncology, Pathology, and Immunology) or more recently in2006–2007 (Hematology).

For the top 7 countries, the top 3 main subject areas in the2006–2007 time period were Biochemistry and molecularbiology, Cell biology, and Oncology, and the share of these3 subject areas (with slight variations in the rankings)ranged from a high of 61.6% for South Korea to 43.6% forGermany (see Table 2). Only China ranked Oncology 1st;the other 6 countries all ranked Biochemistry and molecularbiology 1st.

Evolution of journals publishing MMP-related researchDuring the 3 time periods, the number of journals in-

volved in the MMP scientific literature increased nearlyfivefold (4.9): 188 journals in 1986–1987, 527 in 1996–1997, and 913 in 2006–2007. The top 8 most prolific jour-nals in each of the 3 time periods are presented in Table 4.With a few exceptions (Journal of Biological Chemistry, Bi-ochemical and Biophysical Research Communications, andBiochemical Journal), different journals appear in each timeperiod in varying subject scopes. Although most of the jour-nals of the 1986–1987 time period focused on biologicalchemistry (Journal of Biological Chemistry, Biochemicaland Biophysical Research Communications, BiochemicalJournal, Biochimica et Biophysica Acta, and Biochemistry),half of the journals of the 2006–2007 time period special-ized in cancer research (Cancer Research, Anticancer Re-search, International Journal of Cancer, and Oncogene). It

is worth noting that the concentration of MMP-related pa-pers published in the top 8 journals has been declining:28.4% in 1986–1987, 17.5% in 1996–1997, and 11.9% in2006–2007.

The mean impact factor of the top 8 journals remained ata high level in each time period: 4.30 for 1987, 5.11 for1997, and 5.04 for 2007. In 1987, 2 of the top 8 journalshad impact factors (IFs) >5 (PNAS with 9.38 and Journal ofBiochemistry with 6.37), but by 2007 there were 4 journals(Cancer Research with 7.67, Oncogene with 6.44, Journal ofImmunology with 6.07, and Journal of Biochemistry with 5.58).

For the top 7 countries, all but China listed The Journal ofBiological Chemistry as one of their main journals targetedin the 2006–2007 time period and all but South Korea hadCancer Research as one of the main journals targeted (seeTable 2). The level of concentration in the main journals tar-geted is low: from 7.9% for Germany to 20.4% for SouthKorea. This is reflected by the proliferation of journals overtime (from 188 in 1986–1987 to 913 in 2006–2007), thusscattering papers on MMP-related research throughout manyjournals.

Discussion

General considerationThis study provides a longitudinal overview of research

involving MMPs through a quantitative analysis of the sci-entific literature over two decades (1986–2007). Since 1986,the continuous development of both the understanding of thebasic mechanisms of MMPs and their importance in normaland pathological processes has resulted in dramatic changesin the MMP-related scientific community. From 1986 to2007 the number of publications on MMPs increased morethan sevenfold: 397 articles for 1986–1987 and 2833 for2006–2007 (see Fig. 1), whereas all scientific publicationhad increased by less than twofold. Additionally, the scien-tific community working on MMPs grew substantially, asshown by the doubling of contributing countries from 33 in1986–1987 to 67 in 2006–2007, with most industrializedcountries contributing at least 5 papers each and 27 othercountries contributing fewer than 5 papers each.

Evolution of productive countriesDuring the period considered, the production of MMP-

related research papers was led by the USA. This is not sur-prising, as the USA is the leading contributor in terms ofnumber of publications in all fields of research (Glanzel etal. 2002). This leadership is accompanied by a continuouslydecreasing share of publications: 46.6% for 1986–1987,43.1% for 1996–1997, and 32.3% for 2006–2007. This de-cline is further documented by Shelton and Foland (2009).However, the USA remains a pivotal player in MMP-relatedresearch because it is the main collaborative country of thenext 6 most productive countries (see Table 2), because ithas an impressive number of federally granted projects(72),3 and because of the numerous authoritative reviews

2 As of 1 January 2007, the EU included 27 official Member States.3 Result obtained from a search made on the database CRIPS (Computer Retrieval of Information on Scientific Projects) (http://report.nih.

gov/crisp/CRISPQuery.aspx) for fiscal year 2007, using the following keywords in grant titles: matrixin, collagenase, gelatinase, metallo-proteinase, or MMP.



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Table 2. Publishing profiles of the top 7 most prolific countries involved in MMP-related research for all 3 time periods.

Main collaborators Main subject categories Target journals

CountryNo. ofpapers

No. of collaborativecountries Country

No. ofpapers Category

No. ofpapers Title

No. ofpapers

USA 914 38 Japan 60 Biochemistry and molecular biology 231 Journal of Biological Chemistry 68UK 39 Oncology 150 Cancer Research 38Germany 36 Cell biology 122 Biochemical and Biophysical Research

Communications15

Canada 32 Peripheral vascular disease 61 Investigative Ophthalmology and VisualScience

14

China 26 Neurosciences 59 Oncogene 14Japan 383 25 USA 60 Biochemistry and molecular biology 77 Journal of Biological Chemistry 19

China 16 Cell biology 54 Biochemical and Biophysical ResearchCommunications

11

Germany 6 Oncology 53 Cancer Research 8UK 6 Pharmacy and pharmacology 25 Anticancer Research 7Canada 5 Medicine, research and experimental 22 Life Sciences 7South Korea 5

Germany 227 32 USA 36 Biochemistry and molecular biology 35 Cancer Research 7UK 14 Cell biology 33 Journal of Biological Chemistry 6Belgium 12 Oncology 31 Biological Chemistry 5Switzerland 11 Neurosciences 18Poland 8 Hematology 17

UK 222 30 USA 39 Biochemistry and molecular biology 47 Journal of Biological Chemistry 16Germany 14 Cell biology 27 Prenatal Diagnosis 5Canada 12 Oncology 24 Cancer Research 4Belgium 10 Hematology 17 Cardiovascular Research 4Denmark 8 Cardiac and cardiovascular systems 15

Immunology 15China 202 16 USA 26 Oncology 38 Chinese Medical Journal 10

Japan 16 Biochemistry and molecular biology 35 Cancer Research 7Canada 5 Cell biology 24 World Journal of Gastroenterology 7Taiwan 5 Pharmacy and pharmacology 21 International Journal of Biochemistry 5UK 4 Medicine, research and experimental 14 Toxicon 5South Korea 4

South Korea 172 7 USA 24 Biochemistry and molecular biology 51 Biochemical and Biophysical ResearchCommunications

10

Japan 5 Oncology 28 FEBS Letters 9China 4 Cell biology 27 Journal of Biological Chemistry 6

Pharmacy and pharmacology 25 Archives of Pharmaceutical Research 5Biophysics 20 Journal of Cellular Biochemistry 5

Canada 157 23 USA 32 Biochemistry and molecular biology 39 Journal of Biological Chemistry 11UK 12 Cell biology 31 Journal of Cellular Biology 5France 5 Oncology 19 Cancer Research 4Japan 5 Cardiac and cardiovascular systems 12 Journal of Clinical Endocrinology 4China 5 Immunology 12 Journal of Immunology 4Poland 5 Pharmacy and pharmacology 12 .

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authored by researchers working in the USA (e.g., Hobeikaet al. 2007; Boden and Song 2008; Krane and Inada 2008).

During the 3 time periods, 4 other developed countries(Japan, Germany, the UK, and Canada) were continuouslypresent in the top 7 most prolific countries. These countriesare among the major players and share numerous similaritiesin their MMP publishing profile: a high number of collabo-rative countries with preference for geographical proximityor language, a focus mainly on 3 subject areas (Biochem-istry and molecular analysis, Cell biology, and Oncology),and preference for publishing in certain journals (Journal ofBiological Chemistry or Cancer Research). However, theseprolific countries also differ from one another as shown inTable 2.

The most recent period can be characterized by the ap-pearance of 3 Asian countries in the top 10 publishing coun-tries (China, South Korea, and Taiwan). Their emergencewas also noted in different fields of research such as sleepresearch (Robert et al. 2007), microbiology (Vergidis et al.2005), cardiovascular diseases research (Rosmarakis et al.2005), and otolaryngology (Cimmino et al. 2005), and wasrecently suggested as changing the center of gravity of theworld system of science (Leydesdorff and Zhou 2005). Therecent high ranking of these Asian countries among the ma-jor contributors to research can be attributed to their strongeconomic growth supporting substantial increases in re-search funding over the last decades. This is illustrated par-ticularly by China — over the past 20 years, it has spentapproximately 18 billion Yuan (USD 2.7 billion) in govern-ment funds for more than 100 000 basic research projects(Zhu and Gong 2008). Additionally, the increasing numberof publications by these Asian countries can also be partiallyexplained by financial incentives of national authorities forpublishing in journals indexed by Thomson Scientific. Forexample, South Korea, with only 1 publication in the firstperiod, had 172 papers and ranked 6th in 2006–2007 (seeTable 1). The important role played by South Korea in

MMP-related research is consistent with its dynamism incancer research (Ugolini et al. 2007; Lopez-Illescas et al.2008), and more broadly in various subjects in which re-search can deal with MMPs such as Biology and biochemis-try or Pharmacology and toxicology (Gupta et al. 2007).

It is interesting to examine the publishing profiles ofChina and South Korea in Table 2. First, they have fewercollaborative papers than the other major countries. For ex-ample, China, with 202 papers, had almost the same numberof MMP-related papers as the UK (222) but only had half asmany collaborative countries (16, vs. the UK’s 30). SouthKorea has collaborated with even fewer countries (7); thisperhaps can be attributed to one consequence of the crisistriggered by a great slump in the currency that started at theend of 1997 (Kim 2005). Another note is the preference ofboth countries for collaborating with other Asian countriesafter the USA (see Table 2). Finally, the publishing profileof China is somewhat unique in that two of its most targetedjournals are published in China: Chinese Medical Journaland World Journal of Gastroenterology.

At the other end of productivity, African countries remainunderrepresented; only Tunisia, with 6 papers, ranked in thetop 40 (see Table 1), with 5 other countries having 5 orfewer papers in 2006–2007. The African situation is some-what worrying and confirms results of previous bibliometricscientific literature studies (Rosmarakis et al. 2005; Robertet al. 2007).

Evolution of journal subject areasThe main subject domain targeted by researchers for pub-

lishing their MMP-related papers was Biochemistry and mo-lecular biology for all 3 time periods (see Table 3). This canbe justified by the fact that basic mechanisms of MMPswere mainly investigated using biochemical and molecularbiological approaches (Visse and Nagase 2003; Mott andWerb 2004). Further analysis reveals a decrease of the per-centage of MMP-related papers published in Biochemistry

Table 3. Top 10 subject areas of MMP-related research for 3 time periods: 1986–1987, 1996–1997, and 2006–2007.

1986–1987 1996–1997 2006–2007

Subject areaNo. ofpapers

% (of397) Subject area

No. ofpapers

% (of1518) Subject area

No. ofpapers

% (of2833)

Biochemistry andmolecular biology

160 40.30 Biochemistry andmolecular biology

426 28.06 Biochemistry andMolecular biology

560 19.76

Biophysics 44 11.08 Cell biology 204 13.44 Oncology 411 14.50Cell biology 34 8.56 Oncology 186 12.25 Cell biology 363 12.81Multidisciplinary

sciences27 6.80 Pharmacology and

pharmacy99 6.52 Pharmacology and

pharmacy195 6.88

Rheumatology 23 5.79 Biophysics 88 5.80 Hematology 151 5.33Medicine, research

and experimental21 5.29 Pathology 71 4.68 Peripheral vascular

disease144 5.08

Pharmacology andpharmacy

20 5.04 Immunology 65 4.28 Immunology 141 4.98

Chemistry,multidisciplinary

18 4.53 Medicine, research andexperimental

59 3.89 Neurosciences 133 4.69

Neurosciences 14 3.53 Biotechnology andapplied microbiology

57 3.75 Cardiac andcardiovascularsystems

113 3.99

Surgery 13 3.27 Endocrinology andmetabolism

45 2.96 Pathology 105 3.71



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and molecular biology (40.3% for the period 1986–1987versus 19.8% for 2006–2007). This decline was offset by anincrease in cancer research related to MMPs, with the num-ber of papers more than doubling between 1996–1997 and2006–2007 (see Table 3).

Another important subject area of MMP investigation iscancer research, as illustrated by the concentration of nearly5% (138 publications) of all 2006–2007 MMP-related publi-cations in 4 major cancer-focused journals: Cancer Re-search, Anticancer Research, International Journal ofCancer, and Oncogene (see Table 4). Effectively, MMPsare recognized as playing a major role in the degradation ofthe extracellular matrix, a crucial event for malignant tumorgrowth, invasion, and angiogenesis. The importance ofworks in cancer research has already been mentioned in arecent editorial review (Babjuk 2007) and is further con-firmed by numerous reviews showing the impressive stridesmade from MMP investigations in cancer research (Duffy etal. 2000; Kanayama 2001; Vihinen et al. 2005).

Another subject area attracting MMP investigations is car-diovascular-related research. The importance of MMP re-search linked to this field is illustrated by the 3 differentsubject areas (Hematology, Peripheral vascular diseases, andCardiac and cardiovascular systems) listed among the top 10fields (see Table 3). Indeed, numerous review papers de-scribe the involvement of MMPs in a variety of cardiovascu-lar research areas such as platelet function (Santos-Martınezet al. 2008), peripheral vascular disease (Hobeika et al.2007), post-myocardial infarction (Vanhoutte et al. 2006)and angiogenesis (Rundhauq 2005). Two subject areas re-main of considerable interest in MMP-related researchthroughout the 3 periods: Cell biology, accounting for anaverage of nearly 12% of papers, and Pharmacology andpharmacy, averaging slightly over 6% of papers (see Ta-ble 3). The distribution of publications among the majorMMP-targeted subject areas ranging from fundamental re-search to clinical application and the broad diversity of thesubject areas involved (over 100 in 2006–2007) are healthysigns pointing to the wide interest of the scientific and med-ical communities in MMPs. Furthermore, developments inMMP research are not restricted to the disciplines mentionedhere, but are also of concern in numerous other basic andclinical fields such as oral diseases (Hannas et al. 2007),gastroenterology (Medina and Radomski 2006), and neuro-science (Candelario-Jalil et al. 2009), among others. Addi-tionally, the reader must keep in mind that much researchin MMPs involves multidisciplinary approaches occurring inboth basic and clinical studies, which can span a variety ofscientific disciplines. However, usually only two subjectareas are assigned to each journal, which is generally insuf-ficient to reflect the interdisciplinarity of MMP research.

Evolution of journalsThe evolution of MMP research can also be charted

through the evolution of journals publishing MMP-relatedresearch. The increasing number of journals publishingMMP research during the entire period (from 188 in 1986–1987 to 913 in 2006–2007) is representative of the increas-ing interest in the scientific community for matrixins, andalso for the dissemination of its involvement in a broadspectrum of both clinical and fundamental subject areas. In-T

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deed, an important change in the top-ranked journals tar-geted by MMP-related research was noted during the lastdecades. In the late 1980s, research on MMPs was mainlymade from a biochemical perspective, as illustrated by thepresence of 5 biochemically oriented journals with high vis-ibility and influence (2.39 < IF < 6.37) among the top 8journals: Journal of Biological Chemistry, Biochemical andBiophysical Communications, Biochemical Journal, Biochi-mica et Biophysica Acta, and Biochemistry. Owing to thenumerous advances brought about by MMPs in cancer re-search (Lochter et al. 1998; Scherer et al. 2008), one can ex-pect to see biochemical journals slowly replaced byoncology-oriented journals such as Cancer Research, Anti-cancer Research, International Journal of Cancer, and On-cogene. Despite this shift in interest, it must be noted thatduring all 3 time periods The Journal of Biological Chemis-try, a mainstay for publication of papers in the field of bio-chemistry and molecular biology with a large audience, asevidenced by its high impact factor (5.58 < IF < 6.96), wasthe main journal for the diffusion and dissemination ofMMP-related research. This shows the importance of re-searchers still working on the basic mechanisms of MMPs(Zhao et al. 2008).

Conclusion

This study reveals that during the last two decades (1986–2007), the scientific literature related to MMPs increasedsevenfold. This evolution was characterized by a doublingof contributing countries. Based on the numbers of scientificpublications, the USA continuously ranked first, accompa-nied by Japan, Germany, the UK, Canada, and France. Thelast time period (2006–2007) showed the emergence of 3Asian countries (China, South Korea, and Taiwan) in thetop 10 most productive countries, and the profiles of 7 ofthese top countries include their preferred collaborativecountries and the subject areas of journals targeted for theirMMP-related papers. This study also shows that the majorfields of investigation of MMP-related research have pro-gressively moved from basic research areas (e.g., biochemis-try) to clinical medicine (cancer or cardiovascular research);cell biology and pharmacology remained important avenuesof investigation for researchers over all time periods.

Despite the numerous papers related to MMPs during thelast decades, a great deal still remains to be learned aboutthe precise role of MMPs within each context, including thepotential application of MMP inhibitors as therapeuticagents. It is hoped that the present study showing the rich-ness, importance, and diversity of MMPs in clinical and ex-perimental research provides a useful description of thescientific literature of MMPs and will encourage researchersto further advance this field.

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trends in matrix metalloproteinase research from 1986–2007: a bibliometric study

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