Elsevier

Journal of Biomechanics

Volume 48, Issue 8, 1 June 2015, Pages 1420-1426
Journal of Biomechanics

The role of inflammation in the initiation of osteoarthritis after meniscal damage

https://doi.org/10.1016/j.jbiomech.2015.02.035Get rights and content

Abstract

Meniscal damage and meniscectomy lead to subsequent osteoarthritis (OA) of the knee joint through multiple and diverse mechanisms, yet the interaction of these mechanisms remains unknown. Therefore, the aim of this review is to suggest the multi-scale, multi-faceted components involved between meniscal injury or meniscectomy and the initiation of OA. There is evidence of structural, mechanical, and biological changes after meniscal damage, all of which can be greatly affected by the presence of local or systemic inflammation. Meniscal damage or resection causes changes in knee mechanics during walking, resulting in altered cartilage loading. Because cartilage is mechanically sensitive, these loading changes can initiate a catabolic effect, culminating in tissue degeneration. The evidence suggests that the addition of elevated inflammation at the time of meniscal damage or meniscectomy results in an accelerated progression toward cartilage degradation. Initial cartilage degradation produces inflammation and pain in conjunction with structural changes to the joint, thus perpetuating the cycle of altered cartilage loading and subsequent degradation. Furthermore, the inflammation secondary to obesity and aging introduces an increased risk of developing OA following meniscal injury. Therefore, an overall route between meniscal damage or resection and OA is presented here in a manner that considers two distinct pathways; these pathways reflect the absence or presence of conditions that cause elevated inflammation.

Introduction

Originally thought to be a vestigial organ, modern medicine has recognized the importance of the knee meniscus in joint health (Roos et al., 1998). The meniscal structure, as semi-circular wedges made of fibrocartilage tissue organized with circumferential collagen bundles, allows the tissue to convert compressive joint loads to hoop stresses throughout the meniscus. Additional radially aligned bundles prevent longitudinal tearing of the meniscus (Ishihara et al., 2009). The structure of the meniscal tissue also acts in conjunction with the ligaments of the knee to provide rotational and translation stability between the femur and tibia (Levy et al., 1982). In addition, the mechanobiology of the meniscus plays a role in the activation and mediation of metabolic and inflammatory responses that influence the homeostasis of joint health and conditions that ultimately lead to knee osteoarthritis (OA). Thus the structure, mechanics, and biology of the meniscus contribute to the overall health of the knee joint.

The menisci are susceptible to damage and tears. In the younger population, meniscal tears are typically traumatic and caused by a specific incident such as a sports injury or concomitant ligament rupture (Makris et al., 2011, Metcalf and Barrett, 2004). In the older population, meniscal damage most often presents as degenerative tears and can be symptomatic or asymptomatic (Englund et al., 2008). Longitudinal, “bucket-handle,” and radial tears are classified as traumatic tears, whereas oblique/flap, horizontal, and complex tears (a combination of the aforementioned tear patterns) are classified as degenerative tears (Englund et al., 2001, Scanzello et al., 2011). Root tears are full width tears occurring near the attachment point (root) of the meniscus and can be a traumatic radial tear or a result of meniscal degeneration (Bhatia et al., 2014). The meniscus is often divided into three compartments by labeling convention: the anterior, middle, and posterior thirds (Fig. 1). Depending on the tear type, location, and patient symptoms, meniscal tears can be treated conservatively with physical therapy or weight loss, or surgically with tear repair (peripheral tears only) or meniscectomy (partial or total) (Mezhov et al., 2014). During a partial meniscectomy, only the torn meniscal tissue is removed and the cut edge debrided to prevent further damage or catching, whereas during a total meniscectomy, the entire meniscus is removed (Mezhov et al., 2014). Arthroscopic surgical removal of meniscal tissue is one of the most frequently performed musculoskeletal operations in the United States, with nearly 700,000 procedures annually (Cullen et al., 2009).

Meniscal damage, surgically treated or not, is a known risk factor for the incidence of OA of the knee joint, usually in the same compartment (medial versus lateral) as the damaged tissue. Untreated meniscal damage, including tissue maceration or tearing, is a known risk factor for developing radiographic OA, defined as Kellgren–Lawrence grade 2 or greater, over a 30 month follow up period (odds ratio 5.7) (Englund et al., 2009b). Similarly, a total meniscectomy increases the risk of OA incidence 14-fold in the 21 years post-operation (Roos et al., 1998), whereas a partial meniscectomy increases the risk of OA four-fold in the 16 years post-operation (Englund et al., 2003). While the absolute cause for this increased risk is unknown, it is likely a combination of structural, mechanical, and biological changes that occur due to the tear and resection of tissue (Andriacchi et al., 2004, Berenbaum, 2013, Felson, 2013). Thus, in order to develop clinical treatments or preventative measures for OA onset, it is important to understand how meniscal tears and resection affect the structure, mechanics, and biology of the knee joint, as well as the menisci׳s subsequent ability to provide joint stability, distribute load, and maintain general joint health.

Therefore, the purpose of this review is to develop a multi-scale and multi-faceted pathway between meniscal injury or meniscectomy and the initiation of knee OA. Here, the authors consolidate evidence from the literature regarding changes in the structure, mechanics, and biology of the knee associated with the function of the menisci. The pathway presented here (Fig. 2) considers the presence or absence of local or systemic conditions that cause elevated inflammation in the knee joint at the time of meniscal damage or resection by splitting into pathway A versus pathway B. The suggested pathway is nonetheless applicable when OA is present in the joint at the time of meniscal injury, because, even after OA initiation, inflammation affects subsequent mechanical and biological joint processes (Englund et al., 2009a). Thus, it is suggested that the rate each pathway branch converges to cartilage degradation depends on the interactions of the structural, mechanical, and biological elements of the system.

Section snippets

Inflammation

The literature suggests that there may be chronic inflammation present at the time of meniscal damage (especially during degenerative meniscal tears) and acute inflammation after traumatic meniscal tears. The inflammatory response often occurs with ACL tear, traumatic meniscal tear, and early OA (Englund et al., 2009a). Shortly after an ACL rupture, inflammatory cytokines, specifically IL-1 (interleukin-1) and TNF-α (tumor necrosis factor-alpha), are upregulated in the joint (Lawrence et al.,

Altered gait mechanics (pathway A, the absence of elevated inflammation)

Gait mechanics can be altered by loss of meniscal structural support. Meniscal damage and resection have been directly associated with changes in in vivo knee mechanics (pathway A, Fig. 2). Altering the macrostructure of the meniscus by removing the torn tissue can affect the ability of the menisci to constrain the knee to “normal” motion during daily activities. For example, patients who underwent partial medial meniscectomies had a significant three degree increase in mean external rotation

Altered gait mechanics (pathway B, the presence of elevated inflammation)

Gait mechanics can also change with the loss of structural support combined with elevated levels of proinflammatory cytokines (pathway B, Fig. 2). As previously described, local or systemic inflammation triggers upregulation of inflammatory proteins in the knee, which can cause substantial pain at the knee joint (Berenbaum, 2013). Notably, pain is a known gait modifier, typically causing a decreased knee flexion moment by means of neuromuscular adaptations to avoid pain (Boyer et al., 2012,

Mechanobiology (pathway A, the absence of elevated inflammation)

In the absence of elevated inflammation, joint mechanics play a key role in the development of knee OA. The kinematic and kinetic alterations noted above can cause changes in the location and magnitude of cartilage contact stresses, decreasing load in some regions while increasing load in others. For example, Yang et al. (2009) used two finite element models to test the effects of knee angles in conjunction with meniscal resection on cartilage contact mechanics; one model was a varus aligned

Mechanobiology (pathway B, the presence of elevated inflammation)

In addition to influencing gait mechanics as noted above, inflammation can influence the biological response of cartilage to mechanical load. In vitro work has shown that chondrocytes exhibit significantly different gene expression profiles when subjected to cartilage loading in the presence versus the absence of inflammatory proteins (Bevill et al., 2014). Using pig stifle joint cartilage explants, Bevill et al. (2014) found that chondrocytes displayed an anabolic response to unconfined cyclic

Cartilage degradation

The two pathways (A and B) converge on a common pathway of cartilage degradation that ultimately results in clinical OA. The rate that the joint converges to OA is dependent on the initial changes in gait mechanics and mechanobiology as well as the interaction between the structural, mechanical, and biological conditions associated with injury to the meniscus (Andriacchi et al., 2014). Perhaps more importantly, the rate that the joint converges to clinical OA depends on the joint׳s adaptation

Conflict of interest statement

None of the authors has any conflict of interest regarding the work presented in this manuscript.

Acknowledgments

This work was supported in part by the National Science Foundation Graduate Research Fellowship Program Grant DGE-114747 and by the U.S. Department of Veterans Affairs Grant RX000924. Thank you to the members of the Stanford BioMotion Laboratory for helpful, stimulating conversations.

References (61)

  • E.A. Makris et al.

    The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration

    Biomaterials

    (2011)
  • N.A. Netravali et al.

    Partial medial meniscectomy and rotational differences at the knee during walking

    J. Biomech.

    (2010)
  • H.S. Park et al.

    Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6

    Diabetes Res. Clin. Pract.

    (2005)
  • E. Peña et al.

    Finite element analysis of the effect of meniscal tears and meniscectomies on human knee biomechanics

    Clin. Biomech.

    (2005)
  • F.W. Roemer et al.

    The association of meniscal damage with joint effusion in persons without radiographic osteoarthritis: the Framingham and MOST osteoarthritis studies

    Osteoarthr. Cartil.

    (2009)
  • C.R. Scanzello et al.

    Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease

    Osteoarthr. Cartil.

    (2009)
  • A. Thambyah et al.

    Mechanical properties of articular cartilage covered by the meniscus

    Osteoarthr. Cartil.

    (2006)
  • R. Allaire et al.

    Biomechanical consequences of a tear of the posterior root of the medial meniscus. Similar to total meniscectomy

    J. Bone Jt. Surg. Am.

    (2008)
  • T.P. Andriacchi et al.

    Rotational changes at the knee after ACL injury cause cartilage thinning

    Clin. Orthop. Relat. Res.

    (2006)
  • T.P. Andriacchi et al.

    A systems view of risk factors for knee osteoarthritis reveals insights into the pathogenesis of the disease

    Ann. Biomed. Eng.

    (2014)
  • T.P. Andriacchi et al.

    A framework for the in vivo pathomechanics of osteoarthritis at the knee

    Ann. Biomed. Eng.

    (2004)
  • H. Atmaca et al.

    Changes in the loading of tibial articular cartilage following medial meniscectomy: a finite element analysis study

    Knee Surg. Sports Traumatol. Arthrosc.

    (2013)
  • M. Attur et al.

    Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis

    Arthritis Rheum.

    (2011)
  • A. Bedi et al.

    Dynamic contact mechanics of the medial meniscus as a function of radial tear, repair, and partial meniscectomy

    J. Bone Jt. Surg. Am.

    (2010)
  • S.L. Bevill et al.

    The regional sensitivity of chondrocyte gene expression to coactive mechanical load and exogenous TNF-α stimuli

    J. Biomech. Eng.

    (2014)
  • S. Bhatia et al.

    Meniscal root tears: significance, diagnosis, and treatment

    Am. J. Sports Med.

    (2014)
  • K.A. Boyer et al.

    Sensitivity of gait parameters to the effects of anti-inflammatory and opioid treatments in knee osteoarthritis patients

    J. Orthop. Res.

    (2012)
  • F.P. Cantatore et al.

    Early alteration of synovial membrane in osteoarthrosis

    Clin. Rheumatol.

    (1988)
  • Cullen, K.A., Hall, M.J., Golosinskiy, A., 2009. Ambulatory surgery in the United States, 2006. National Health...
  • A. Durand et al.

    Motor recovery after arthroscopic partial meniscectomy

    J. Bone Jt. Surg. Am.

    (1993)
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