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Commentary and Perspective   |    
The Meniscus—A Key to Unfolding the Mystery of OsteoarthritisCommentary on an article by Robert H. Brophy, MD, et al.: “Molecular Analysis of Age and Sex-Related Gene Expression in Meniscal Tears with and without a Concomitant Anterior Cruciate Ligament Tear”
Helen Kambic, PhD
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This article was chosen to appear electronically on February 22, 2012, in advance of publication in a regularly scheduled issue.



Disclosure: The author received no payments or services, either directly or indirectly (i.e., via her institution), from a third party in support of any aspect of this work. Neither the author nor her institution has had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, the author has not had any other relationships, or engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Mar 07;94(5):e31 1-2. doi: 10.2106/JBJS.K.01593
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Our appreciation of the molecular organization of the meniscus is leading to a greater understanding of its cellular function in disease. Meniscal tears can lead to knee osteoarthritis, but knee osteoarthritis can lead to a spontaneous meniscal tear through breakdown of the meniscal structure1. This study is timely and relevant regarding the predicted increase in the prevalence of new cases of osteoarthritis in the young athletic population of both sexes. The cross-reactivity of several molecular markers associated with osteoarthritis was demonstrated in the torn meniscus. Although the authors chose an age cutoff of forty years, the age at onset of meniscal injury influences the primary cellular response. Age-related changes coupled with tear location within the meniscus and contributions of the synovial fluid could influence gene expression.
There is ample evidence that the meniscus has a related but distinct molecular signature that is different from that found in articular cartilage. The collagen ultrastructure places the meniscus at risk for longitudinal tears. Torn menisci and concomitant anterior cruciate ligament (ACL) rupture possess unique and specific phenotypic cells and gene expression with combined injuries. One study has noted that genes detected from osteoarthritic meniscal cells differ from normal meniscal cells and are abnormally expressed in other types of osteoarthritic cells or tissues, which suggests that differential gene expressions detected may be age-related and/or disease-specific2.
The meniscal status at the time of surgery has been considered an important factor for predicting the development of osteoarthritis3. Attention is now directed to the identification of biomarkers of key catabolic activities within the torn meniscus. In this study, the authors are to be commended for focusing on the gene expression profiles found in the meniscus subject to time-varying changes in mechanical effects due to meniscal tears and for analyzing the correlation between this damage to combined tears in both the meniscus and ACL. Meniscal tissue was retrieved at the time of partial meniscectomy and divided by sex and age (under and over forty years of age). This approach avoided the changes introduced by cell culture conditions and was validated by quantitative real-time polymerase chain reaction methods and rigorous statistical analyses.
The rationale for the use of the cutoff of forty years of age was based on the fact that torn menisci in mature patients have lower cellularity. More male patients presented with meniscal tears and combined injury in both age groups. These could be the result of participation in more aggressive sports and manual activities. In other reports, increased age, male sex, and surgical delay increased the frequency and severity of injuries of the meniscus and/or articular cartilage after an ACL tear4.
The authors point out that the meniscus in younger patients reacts with an intrinsic response and is more prone to inflammatory changes. Intrinsic meniscal degeneration occurs in both men and women and begins at about thirty years of age; degenerative meniscal tears occur in association with age-related degenerative changes in the tissue5. A tear to the meniscus alters the fibrochondrocytes experiencing the compressive forces at the inner half of the meniscus and subsequently also influences the fibroblast or superficial zone cell metabolism. Evidence for the cross-reactivity of interleukin-1β (IL-1β)-mediated increases in matrix metalloproteinase (MMP) activity is evident in both the meniscal tear and with combined tears in individuals under the age of forty years. Aggrecan expression associated with inflammatory cytokines was lower in patients under forty years of age with combined tears. The response to meniscal injury may be dependent not only on these cells but also on a subpopulation of cells expressing a remodeling response to injury5.
What is unique to the study is that in the group of patients over forty years old, there were no differences in inflammatory cytokines or chemokines. An increased expression of the chemokine CCL3L1 was found in meniscal tears in both male and female patients; however, this significantly increased in females with combined injury. The combined injury results in more severe damage to the joint than the result of a single meniscal lesion. Remarkably, there were no significant differences among the other genes based on sex and injury. It would be interesting to know if these markers are consistent over a greater population of patients with precise identification of the extent of damage to either or both the lateral or medial meniscus. If confirmed in larger studies, these markers may monitor local events at the surgical sites and detect the progression of osteoarthritis. In summary, this article suggests that there may be more information hidden in the meniscus than previously thought.
Englund  M;  Guermazi  A;  Lohmander  SL. The role of the meniscus in knee osteoarthritis: a cause or consequence?Radiol Clin North Am.  2009;47:703-12.
 
Sun  Y;  Mauerhan  DR;  Honeycutt  PR;  Kneisl  JS;  Norton  JH;  Hanley  EN  Jr;  Gruber  HE. Analysis of meniscal degeneration and meniscal gene expression. BMC Musculoskelet Disord.  2010;11:19.
 
Shelbourne  KD;  Gray  T. Results of anterior cruciate ligament reconstruction based on meniscus and articular cartilage status at the time of surgery. Five- to fifteen-year evaluations. Am J Sports Med.  2000;28:446-52.
 
Slauterbeck  JR;  Kousa  P;  Clifton  BC;  Naud  S;  Tourville  TW;  Johnson  RJ;  Beynnon  BD. Geographic mapping of meniscus and cartilage lesions associated with anterior cruciate ligament injuries. J Bone Joint Surg Am.  2009;91:2094-103.
 
Rodeo  SA;  Kawamura  S. Form and function of the meniscus.  In: Einhorn  TA;  O'Keefe  RJ;  Buckwalter  JA,  editors. Orthopaedic basic science. 3rd ed. Rosemont: American Academy of Orthopaedic Surgeons; 2007. p 175-89.
 

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References

Englund  M;  Guermazi  A;  Lohmander  SL. The role of the meniscus in knee osteoarthritis: a cause or consequence?Radiol Clin North Am.  2009;47:703-12.
 
Sun  Y;  Mauerhan  DR;  Honeycutt  PR;  Kneisl  JS;  Norton  JH;  Hanley  EN  Jr;  Gruber  HE. Analysis of meniscal degeneration and meniscal gene expression. BMC Musculoskelet Disord.  2010;11:19.
 
Shelbourne  KD;  Gray  T. Results of anterior cruciate ligament reconstruction based on meniscus and articular cartilage status at the time of surgery. Five- to fifteen-year evaluations. Am J Sports Med.  2000;28:446-52.
 
Slauterbeck  JR;  Kousa  P;  Clifton  BC;  Naud  S;  Tourville  TW;  Johnson  RJ;  Beynnon  BD. Geographic mapping of meniscus and cartilage lesions associated with anterior cruciate ligament injuries. J Bone Joint Surg Am.  2009;91:2094-103.
 
Rodeo  SA;  Kawamura  S. Form and function of the meniscus.  In: Einhorn  TA;  O'Keefe  RJ;  Buckwalter  JA,  editors. Orthopaedic basic science. 3rd ed. Rosemont: American Academy of Orthopaedic Surgeons; 2007. p 175-89.
 
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