Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Integrative Biology

Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus

International Journal of Obesity volume 37, pages 1238–1246 (2013)Cite this article

Subjects

Abstract

Objective:

Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus.

Design:

Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expression of 24 osteoarthritis-related and 4 obesity-related genes in meniscus was assessed by quantitative real-time PCR. The relationship between gene expression and patient age and BMI was analyzed using Spearman’s rank–order correlation. Hierarchical cluster dendrogram and heat map were generated to study inter-gene associations.

Results:

Age was negatively correlated (P<0.05) with the expression of MMP-1 (r=−0.447), NFκB2 (r=−0.361), NFκBIA (r=−0.312), IκBA (r=−0.308), IL-8 (r=−0.305), ADAMTS-4 (r=−0.294), APLN (apelin) (r=−0.250) and IL-6 (r=−0.244). Similarly, BMI was negatively correlated with the expression of APLN (r=−0.328), ACAN (r=−0.268) and MMP-1 (r=−0.261). After adjusting for the correlation between age and BMI (r=0.310; P=0.008), the only independent effect of BMI on gene expression was for APLN (r=−0.272). However, age had an independent effect on the expression on ADAMTS-4 (r=−0.253), MMP-1 (r=−0.399), IL-8 (r=−0.327), COL1A1 (r=−0.287), NFκBIA (r=−0.278), NFκB2 (r=−0.312) and IκBA (r=−0.299). The gene correlation analysis identified four clusters of potentially relevant genes: transcription factors, matrix-degrading enzymes, cytokines and chemokines, and obesity genes.

Conclusion:

Age and BMI were negatively correlated with several osteoarthritis- and obesity-related genes. Although the bulk of these changes appeared to be driven by age, expression of APLN was related to BMI. Inter-gene correlation analysis implicated a common role for strongly correlated genes. Although age-related variations in gene expression appear to be more relevant than obesity-related differences for the role of the meniscus in osteoarthritis development, further investigation into the role of APLN in meniscus and joint health is warranted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Woolf AD, Pfleger B . Burden of major musculoskeletal conditions. Bull World Health Organiz 2003; 81: 646–656.

    Google Scholar 

  2. van Baar ME, Dekker J, Lemmens JA, Oostendorp RA, Bijlsma JW . Pain and disability in patients with osteoarthritis of hip or knee: the relationship with articular, kinesiological, and psychological characteristics. J Rheumatol 1998; 25: 125–133.

    CAS  PubMed  Google Scholar 

  3. Brandt KD, Radin EL, Dieppe PA, van de Putte L . Yet more evidence that osteoarthritis is not a cartilage disease. Ann Rheum Dis 2006; 65: 1261–1264.

    Article  CAS  Google Scholar 

  4. Loeser RF, Goldring SR, Scanzello CR, Goldring MB . Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64: 1697–1707.

    Article  Google Scholar 

  5. Loeser RF . Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin Geriatr Med 2010; 26: 371–386.

    Article  Google Scholar 

  6. Walker PS, Erkman MJ . The role of the menisci in force transmission across the knee. Clin Orthop Relat Res 1975; 109: 184–192.

    Article  Google Scholar 

  7. Masouros SD, McDermott ID, Amis AA, Bull AM . Biomechanics of the meniscus-meniscal ligament construct of the knee. Knee Surg Sports Traumatol Arthrosc 2008; 16: 1121–1132.

    Article  CAS  Google Scholar 

  8. Englund M, Guermazi A, Lohmander LS . The meniscus in knee osteoarthritis. Rheum Dis Clin North Am 2009; 35: 579–590.

    Article  Google Scholar 

  9. Chevrier A, Nelea M, Hurtig MB, Hoemann CD, Buschmann MD . Meniscus structure in human, sheep, and rabbit for animal models of meniscus repair. J Orthop Res 2009; 27: 1197–1203.

    Article  Google Scholar 

  10. Macconaill MA . The function of intra-articular fibrocartilages, with special reference to the knee and inferior radio-ulnar joints. J Anat 1932; 66: 210–227.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Messner K, Gao J . The menisci of the knee joint. Anatomical and functional characteristics, and a rationale for clinical treatment. J Anat 1998; 193: 161–178.

    Article  CAS  Google Scholar 

  12. Renstrom P, Johnson RJ . Anatomy and biomechanics of the menisci. Clin Sports Med 1990; 9: 523–538.

    CAS  PubMed  Google Scholar 

  13. Mow VC, Holmes MH, Lai WM . Fluid transport and mechanical properties of articular cartilage: a review. J Biomech 1984; 17: 377–394.

    Article  CAS  Google Scholar 

  14. Lim SY, Peh WC . Magnetic resonance imaging of sports injuries of the knee. Ann Acad Med 2008; 37: 354–361.

    Google Scholar 

  15. Hayes CW, Coggins CA . Sports-related injuries of the knee: an approach to MRI interpretation. Clin Sports Med 2006; 25: 659–679.

    Article  Google Scholar 

  16. McDermott ID, Amis AA . The consequences of meniscectomy. J Bone Joint Surg Br 2006; 88: 1549–1556.

    Article  CAS  Google Scholar 

  17. Englund M . The role of the meniscus in osteoarthritis genesis. Rheum Dis Clin North Am 2008; 34: 573–579.

    Article  Google Scholar 

  18. Englund M, Guermazi A, Lohmander SL . The role of the meniscus in knee osteoarthritis: a cause or consequence? Radiol Clin North Am 2009; 47: 703–712.

    Article  Google Scholar 

  19. Englund M . Meniscal tear--a feature of osteoarthritis. Acta orthopaedica Scandinavica. Supplementum 2004; 75: 1–45.

    Google Scholar 

  20. Ding C, Martel-Pelletier J, Pelletier JP, Abram F, Raynauld JP, Cicuttini F et al. Meniscal tear as an osteoarthritis risk factor in a largely non-osteoarthritic cohort: a cross-sectional study. J Rheumatol 2007; 34: 776–784.

    PubMed  Google Scholar 

  21. Zeichen J, Hankemeier S, Knobloch K, Jagodzinski M . [Arthroscopic partial meniscectomy]. Oper Orthop Traumatol 2006; 18: 380–392.

    Article  Google Scholar 

  22. Noble J, Hamblen DL . The pathology of the degenerate meniscus lesion. J Bone Joint Surg Br 1975; 57: 180–186.

    Article  CAS  Google Scholar 

  23. Casscells SW . The torn or degenerated meniscus and its relationship to degeneration of the weight-bearing areas of the femur and tibia. Clin Orthop Relat Res 1978; 132: 196–200.

    Google Scholar 

  24. Lewandrowski KU, Muller J, Schollmeier G . Concomitant meniscal and articular cartilage lesions in the femorotibial joint. Am J Sports Med 1997; 25: 486–494.

    Article  CAS  Google Scholar 

  25. Bennett LD, Buckland-Wright JC . Meniscal and articular cartilage changes in knee osteoarthritis: a cross-sectional double-contrast macroradiographic study. Rheumatology 2002; 41: 917–923.

    Article  CAS  Google Scholar 

  26. Brophy RH, Matava MJ . Surgical options for meniscal replacement. J Am Acad Orthop Surg 2012; 20: 265–272.

    Article  Google Scholar 

  27. Howell JR, Handoll HH . Surgical treatment for meniscal injuries of the knee in adults. Cochrane Database Syst Rev 2000; CD001353.

  28. Paxton ES, Stock MV, Brophy RH . Meniscal repair versus partial meniscectomy: a systematic review comparing reoperation rates and clinical outcomes. Arthroscopy 2011; 27: 1275–1288.

    Article  Google Scholar 

  29. Andersson-Molina H, Karlsson H, Rockborn P . Arthroscopic partial and total meniscectomy: a long-term follow-up study with matched controls. Arthroscopy 2002; 18: 183–189.

    Article  Google Scholar 

  30. Hede A, Larsen E, Sandberg H . Partial versus total meniscectomy. A prospective, randomised study with long-term follow-up. J Bone Joint Surg Br 1992; 74: 118–121.

    Article  CAS  Google Scholar 

  31. Aigner T, Richter W . OA in 2011: Age-related OA--a concept emerging from infancy? Nat Rev Rheumatol 2012; 8: 70–72.

    Article  Google Scholar 

  32. Lohmander LS, Gerhardsson de Verdier M, Rollof J, Nilsson PM, Engstrom G . Incidence of severe knee and hip osteoarthritis in relation to different measures of body mass: a population-based prospective cohort study. Ann Rheum Dis 2009; 68: 490–496.

    Article  CAS  Google Scholar 

  33. Lementowski PW, Zelicof SB . Obesity and osteoarthritis. Am J Orthop 2008; 37: 148–151.

    PubMed  Google Scholar 

  34. Lotz M, Loeser RF . Effects of aging on articular cartilage homeostasis. Bone 2012; 51: 241–248.

    Article  CAS  Google Scholar 

  35. Jiang L, Rong J, Wang Y, Hu F, Bao C, Li X et al. The relationship between body mass index and hip osteoarthritis: a systematic review and meta-analysis. Joint Bone Spine 2011; 78: 150–155.

    Article  Google Scholar 

  36. Rai MF, Sandell LJ . Inflammatory mediators: tracing links between obesity and osteoarthritis. Critical Rev Euk Gene Expr 2011; 21: 131–142.

    Article  CAS  Google Scholar 

  37. Pottie P, Presle N, Terlain B, Netter P, Mainard D, Berenbaum F . Obesity and osteoarthritis: more complex than predicted!. Ann Rheum Dis 2006; 65: 1403–1405.

    Article  CAS  Google Scholar 

  38. Sharma L, Chang A . Overweight: advancing our understanding of its impact on the knee and the hip. Ann Rheum Dis 2007; 66: 141–142.

    Article  Google Scholar 

  39. Brophy RH, Rai MF, Zhang Z, Torgomyan A, Sandell LJ . Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear. J Bone Joint Surg Am 2012; 94: 385–393.

    Article  Google Scholar 

  40. Rosner IA, Goldberg VM, Moskowitz RW . Estrogens and osteoarthritis. Clin Orthop Relat Res 1986; 213: 77–83.

    CAS  Google Scholar 

  41. Verbrugge LM . Women, men, and osteoarthritis. Arthritis Care Res 1995; 8: 212–220.

    Article  CAS  Google Scholar 

  42. Geiger K, Muendlein A, Stark N, Saely CH, Wabitsch M, Fraunberger P et al. Hypoxia induces apelin expression in human adipocytes. Horm Metab Res 2011; 43: 380–385.

    Article  CAS  Google Scholar 

  43. Nohira T, Nagao K, Kameyama K, Nakai H, Fukumine N, Okabe K et al. Identification of an alternative splicing transcript for the resistin gene and distribution of its mRNA in human tissue. Eur J Endocrinol 2004; 151: 151–154.

    Article  CAS  Google Scholar 

  44. Hu PF, Chen WP, Tang JL, Bao JP, Wu LD . Apelin plays a catabolic role on articular cartilage: in vivo and in vitro studies. Int J Mol Med 2010; 26: 357–363.

    CAS  PubMed  Google Scholar 

  45. Kleinz MJ, Davenport AP . Emerging roles of apelin in biology and medicine. Pharmacol Ther 2005; 107: 198–211.

    Article  CAS  Google Scholar 

  46. Rayalam S, Della-Fera MA, Krieg PA, Cox CM, Robins A, Baile CA . A putative role for apelin in the etiology of obesity. Biochem Biophys Res Commun 2008; 368: 815–819.

    Article  CAS  Google Scholar 

  47. Xie H, Yuan LQ, Luo XH, Huang J, Cui RR, Guo LJ et al. Apelin suppresses apoptosis of human osteoblasts. Apoptosis 2007; 12: 247–254.

    Article  CAS  Google Scholar 

  48. Scheller G, Sobau C, Bulow JU . Arthroscopic partial lateral meniscectomy in an otherwise normal knee: Clinical, functional, and radiographic results of a long-term follow-up study. Arthroscopy 2001; 17: 946–952.

    Article  CAS  Google Scholar 

  49. Loeser RF, Olex AL, McNulty MA, Carlson CS, Callahan MF, Ferguson CM et al. Microarray analysis reveals age-related differences in gene expression during the development of osteoarthritis in mice. Arthritis Rheum 2012; 64: 705–717.

    Article  CAS  Google Scholar 

  50. Mesiha M, Zurakowski D, Soriano J, Nielson JH, Zarins B, Murray MM . Pathologic characteristics of the torn human meniscus. Am J Sports Med 2007; 35: 103–112.

    Article  Google Scholar 

  51. Sun Y, Mauerhan DR, Honeycutt PR, Kneisl JS, Norton JH, Hanley EN et al. Analysis of meniscal degeneration and meniscal gene expression. BMC Musculoskelet Disord 2010; 11: 19.

    Article  Google Scholar 

  52. Sandell LJ, Xing X, Franz C, Davies S, Chang LW, Patra D . Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1ß. Osteoarthritis Cartilage 2008; 16: 1560–1571.

    Article  CAS  Google Scholar 

  53. Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA . Early changes in lapine menisci during osteoarthritis development: Part II: molecular alterations. Osteoarthritis Cartilage 2001; 9: 65–72.

    Article  CAS  Google Scholar 

  54. Eggli S, Wegmuller H, Kosina J, Huckell C, Jakob RP . Long-term results of arthroscopic meniscal repair. An analysis of isolated tears. Am J Sports Med 1995; 23: 715–720.

    Article  CAS  Google Scholar 

  55. Kotsovolos ES, Hantes ME, Mastrokalos DS, Lorbach O, Paessler HH . Results of all-inside meniscal repair with the FasT-Fix meniscal repair system. Arthroscopy 2006; 22: 3–9.

    Article  Google Scholar 

  56. Brindle T, Nyland J, Johnson DL . The meniscus: review of basic principles with application to surgery and rehabilitation. J Athl Train 2001; 36: 160–169.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Issa RI, Griffin TM . Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation. Pathobiol Aging Age Rel Dis 2012; 2: 17470.

    Article  CAS  Google Scholar 

  58. Mork PJ, Holtermann A, Nilsen TI . Effect of body mass index and physical exercise on risk of knee and hip osteoarthritis: longitudinal data from the Norwegian HUNT Study. J Epidemiol Community Health 2012; 66: 678–683.

    Article  Google Scholar 

  59. Spindler KP, Miller RR, Andrish JT, McDevitt CA . Comparison of collagen synthesis in the peripheral and central region of the canine meniscus. Clin Orthop Relat Res 1994; 303: 256–263.

    Google Scholar 

  60. Fuller ES, Smith MM, Little CB, Melrose J . Zonal differences in meniscus matrix turnover and cytokine response. Osteoarthritis Cartilage 2012; 20: 49–59.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Funding for this study was provided by an Orthopaedic Research and Education Foundation (OREF) grant (RHB), National Institute of Arthritis and Musculoskeletal and Skin Diseases grant RO1-AR036994 (LJS) and Musculoskeletal Research Center, grant P30-AR057235. MFR is supported by Ruth L Kirschstein National Research Service Award Fellowship (T32-AR060719) from National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Arthritis, Musculoskeletal and Skin Diseases or the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, MO, USA

    M F Rai, L J Sandell & R H Brophy

  2. Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, MO, USA

    L J Sandell

  3. Department of Anatomy and Neurobiology, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, MO, USA

    J M Cheverud

Authors
  1. M F Rai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L J Sandell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J M Cheverud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R H Brophy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R H Brophy.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rai, M., Sandell, L., Cheverud, J. et al. Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus. Int J Obes 37, 1238–1246 (2013). https://doi.org/10.1038/ijo.2012.221

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2012.221

Keywords

Search

Advanced search

Quick links