Subject: Osteoarthritis in the Patellofemoral Joint (FULL TEXT)
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Osteoarthritis: What We Have Been Missing in the Patellofemoral Joint
Andrea L. Clark
Exerc Sport Sci Rev. 2008;36(1):30-37. ©2008 American College of Sports Medicine
Abstract and Introduction
Patellofemoral osteoarthritis is common clinically and often independent of tibiofemoral disease. Intriguingly, the patella demonstrates more severe degeneration earlier in the disease process compared with the juxtaposed femoral groove. Here, we consider three hypotheses influencing this disparity and thus discover crucial insights into the etiology of osteoarthritis.
Osteoarthritis. Osteoarthritis is a joint disease currently affecting 14 million Americans, a similar number of Europeans, and approximately half as many Japanese. These patient numbers are projected to increase into the year 2012. Risk factors for osteoarthritis include age, obesity, genetic factors, and joint injury or trauma. Joints most often affected by osteoarthritis include the hip, knee, and metatarsophalangeal joints of the lower limb. The spine and the distal and proximal interphalangeal joints of the hand are also frequently affected. The most common signs and symptoms of osteoarthritis include joint soreness, stiffness, and pain especially after periods of overuse or inactivity. Patients may feel grating or catching when they move an affected joint. Osteoarthritic joints may be inflamed and have a thickened capsule, bone spurs, and/or damage to other soft tissues including the articular cartilage. Cartilage damage can involve a loss of surface integrity including fibrillation and fissuring. Spherical and clustered chondrocytes and a loss of proteoglycan molecules at the surface of the tissue may also be evident. With severe disease, there may be complete loss of articular cartilage resulting in bone-on-bone articulation in the joint. Presently, there is no treatment available to physicians to slow down or stop the progression of osteoarthritis. Treatment options include encouraging weight loss and exercise for patients and prescribing increasingly stronger drugs to combat pain. Ultimately, patients undergo joint replacement surgery.
Knee Osteoarthritis - What Happened to the Patellofemoral Compartment? One of the joints most often affected by osteoarthritis is the knee. The knee is a complex joint consisting of three compartments: the patellofemoral and the medial and lateral tibiofemoral compartments. The patella is a dynamic sesamoid bone embedded in the quadriceps tendon articulating directly with the femoral groove to form the patellofemoral joint. Forces up to eight times the body weight can be transferred across the congruent patellofemoral joint during everyday activities. In contrast, the tibiofemoral joint is noncongruent and uses menisci, ligaments, and muscles to improve stability. Despite the considerable contribution of all three compartments to knee articulation and force transfer to the lower limb, most studies investigating knee osteoarthritis have focused on the tibiofemoral compartments with only limited reporting on the patellofemoral compartment.
In large clinical surveys of knee osteoarthritis, there is a lack of data addressing patellofemoral disease and its correlation to tibiofemoral disease. This has been attributed to the use of anteroposterior, but not lateral, knee radiographs in these studies. The choice of radiograph may have been influenced, in part, by the historical work of Kellgren and Lawrence that used a single anteroposterior x-ray view to diagnose knee osteoarthritis. Financial constraints and the importance of avoiding radiation hazard were discussed as the radiographic limiting factors in their study. As with clinical studies, research involving animal models of osteoarthritis has paid much more attention to the tibiofemoral compartments compared with the patellofemoral compartment. Many of the animal models of knee osteoarthritis are based on surgical disruption of soft tissues such as the menisci or cruciate ligaments. It is perhaps intuitive that investigators using these models would focus their attention on the tibiofemoral compartments as opposed to the patellofemoral compartment because of proximity to the disrupted soft tissue.
A sample of literature from our work[7,8] and those of others[11,18,23-25,28] highlighting patellofemoral osteoarthritis both in human and animal subjects will be discussed below. Basing from these studies, I suggest that the patellofemoral joint should no longer be disregarded in studies of knee joint osteoarthritis and that, in fact, the disparity of the disease across the articulating surfaces of this joint may hold crucial insights into the etiology of osteoarthritis.
Disparate Patellofemoral Osteoarthritis
McAlindon et al., obtained weight-bearing anteroposterior knee radiographs and recumbent lateral knee radiographs from knee pain-positive patients (n = 273) and a selection of asymptomatic controls (n = 240). A "knee pain-positive" designation was given to a positive response to two questions: (i) have you ever had pain in or around a knee on most days for at least a month? (ii) if so, have you had any knee pain during the last year? To address the potential for increased variability in scoring patellofemoral as compared with tibiofemoral osteoarthritis, the radiographs were given a simple "on-off" measure of osteoarthritis. This followed the principles of Kellgren and Lawrence, with joint space narrowing being mandatory for the designation of osteoarthritis.
From the seven potential patterns of osteoarthritis distribution throughout the tricompartmental knee, only three were common: lone medial, lone patellofemoral, and medial/patellofemoral compartment overlap (Figure 1). Among knee pain-positive male subjects, lone medial compartment disease was the most common pattern, and it increased in frequency with age (Figure 1). Among knee pain-positive female subjects, lone patellofemoral osteoarthritis was most common and also tended to increase in frequency with age (Figure 1). The third most common pattern, medial/patellofemoral disease, had similar prevalence in male and female subjects (Figure 1). Finally, both medial and patellofemoral osteoarthritis were strongly associated with disability as assessed using the lower limb components of the health assessment questionnaire.
Frequency of compartmental patterns of knee osteoarthritis in knee pain-positive (+) male (M) and female (F) subjects and a knee pain-negative (-) subgroup. Medial/Lateral indicates medial/lateral tibiofemoral joint; PFJ, patellofemoral joint. [Adapted from McAlindon, T.E., S. Snow, C. Cooper, and P.A. Dieppe. Radiographic patterns of osteoarthritis of the knee joint in the community: the importance of the patellofemoral joint. Ann. Rheum. Dis. 51:844-849, 1992. Copyright © 1992 BMJ Publishing Group Ltd. Used with permission.]
In addition to radiographic evidence, focal cartilage or full-thickness cartilage/bone defects have been reported in the patellofemoral joints of patients undergoing surgery and autopsy.[11,18,24,25,28] For example, in one autopsy series, 92 of 98 individuals (aged 4-94 yr) demonstrated either overt cartilage fibrillation or full-thickness cartilage loss covering 5%-100% of the patellofemoral surfaces. Of 1000 consecutive knee arthroscopies, 14% demonstrated softening and swelling defects, and 3% demonstrated focal lesions in the patellofemoral cartilage. In this study, it was further noted that patients with lesions frequently had an associated meniscal and/or ligament injury. In addition to frequency, the disparity of cartilage defects across the juxtapose cartilage surfaces of the patellofemoral joint was also noted. Differences in human patellar cartilage including fibrillation, fissuring, softening, and swelling occurred at an earlier age, were more severe, and covered a larger portion of the cartilage surface on the patella compared with the femoral groove. This observation was consistent for subjects undergoing autopsy and surgery.[11,18,24,25,28]
Feline Anterior Cruciate Ligament Transection Model
Surgical section of the anterior cruciate ligament is perhaps the most thoroughly characterized animal model of osteoarthritis. This model has been studied in a wide variety of animal species including the dog, cat, rat, and rabbit. Work involving the dog and cat has enabled some of the more clinical manifestations of osteoarthritis, such as changes to gait patterns, joint instability, and load redistribution within and between joints, to be evaluated in parallel to the histological, biochemical, and metabolic pathology.[14-17,29] These models have been used extensively to study the early changes after anterior cruciate ligament transection (ACLT); however, only rarely have the animals been maintained long term to study the later osteoarthritic adaptations to this joint injury.
The patellofemoral joints of cats were inspected at 4 months (n = 6) and 5 yr (n = 6) postunilateral ACLT.[7,8] At 4 months, half of the experimental patellae contained small erosions, the most severe being a full-thickness defect. Experimental patellar cartilage was thicker (P < 0.05) and contained more three-cell clusters of superficial and middle layer chondrocytes (P < 0.001) compared with contralateral tissue (Figure 2). In contrast, there were no significant differences between the experimental and contralateral femoral grooves (Figure 2).
Typical histological sections of patellar and femoral groove articular cartilage taken from a normal healthy feline, the contralateral and experimental hind limbs of one animal 4 months postunilateral anterior cruciate ligament transection (ACLT) and another animal 5 yr post-ACLT. The superficial (S), middle (M), and deep (D) cartilage zones are marked to the left of each section. All sections are 0.5-µm thick, stained with toluidine blue, and photographed at 50x magnification. Note the progressive adaptation of patellar but not femoral groove cartilage over time post-ACLT. At 4 months, patellar cartilage is thicker and contains larger and more frequently clustered chondrocytes in the middle zone compared with normal patellar tissue. At 5 yr, patellar cartilage is even thicker and has an uneven contact surface, with loss of proteoglycan staining and clustering of chondrocytes in the superficial and middle zones. [Adapted from Clark, A.L., T.R. Leonard, L.D. Barclay, J.R. Matyas, and W. Herzog. Opposing cartilages in the patellofemoral joint adapt differently to long-term cruciate deficiency: chondrocyte deformation and reorientation with compression. Osteoarthritis Cartilage. 13:1100-1114, 2005. Copyright © 2005 Elsevier Limited. Used with permission.] [Adapted from Clark, A.L., T.R. Leonard, L.D. Barclay, J.R. Matyas, and W. Herzog. Heterogeneity in patellofemoral cartilage adaptation to anterior cruciate ligament transection; chondrocyte shape and deformation with compression. Osteoarthritis Cartilage 14:120-130, 2006. Copyright © 2006 Elsevier Limited. Used with permission.]
Five years post-ACLT, full- or partial-thickness cartilage erosions were observed at the distal poles of two experimental and one contralateral patellae. Microscopically, experimental patellae were thicker (P < 0.01), had an uneven contact surface, and contained rounded chondrocytes in columns and clusters throughout the depth of the cartilage (Figure 2). The proteoglycan staining was unevenly distributed throughout tissue depth, being greatly depleted in the top third of the cartilage (Figure 2). Five of six contralateral patellae demonstrated similar disparities as described for the experimental patellae, although generally to a lesser extent (Figure 2). Histological parameters were quantified in these animals using the Mankin et al. histological-histochemical grading scheme substituting toluidine blue for safranin O as the metachromatic dye, indicating the presence of proteoglycans in the cartilage matrix. This scale gives a score range of 0-14 points, with 14 being the most damaged cartilage. Using this scale, the patellar histological-histochemical scores ranged from zero to eight (Figure 3). In complete contrast, only one experimental femoral groove demonstrated full-thickness cartilage erosion. All contralateral and four of the six experimental femoral grooves seemed normal histologically, with histological-histochemical scores from zero to two (Figure 2, 3). The surfaces were flat, with normal cartilage and chondrocyte architecture and with proteoglycan staining evenly distributed throughout (Figure 2).
Totaled scores from a modified Mankin et al. histological-histochemical grading scheme applied to patellar (pat) and femoral groove (fem) cartilages from contralateral (contra) and experimental (exp) hind limbs from six 5-yr post-anterior cruciate ligament transection (ACLT) felines. The Mankin et al. scale gives a score range of 0-14 points, with 14 being the most osteoarthritic cartilage. Note the larger scores of patellar compared with femoral groove cartilages. Bub, Dud, Kra, Mur, Cas, Pav are ID labels for the six feline subjects. [Adapted from Clark, A.L., T.R. Leonard, L.D. Barclay, J.R. Matyas, and W. Herzog. Opposing cartilages in the patellofemoral joint adapt differently to longterm cruciate deficiency: chondrocyte deformation and reorientation with compression. Osteoarthritis Cartilage 13:1100-1114, 2005. Copyright © 2005 Elsevier Limited. Used with permission.]
These human and animal studies highlight the importance of considering the patellofemoral compartment in studies of knee osteoarthritis. Patellofemoral osteoarthritis is common in both men and women, associated with disability, and frequently independent of tibiofemoral disease. Furthermore, the disparity of patellofemoral osteoarthritis across the articulating surfaces of the joint is intriguing. In both human and animal subjects, softening, fibrillation, proteoglycan loss, and chondrocyte clustering occur earlier in the disease process, are more severe, and cover a larger portion of the cartilage surface of the patella compared with the femoral groove. Careful consideration of the mechanics of the patellofemoral joint and differences between patellar and femoral groove cartilages may hold crucial insights into the etiology of osteoarthritis. In the following discussion, we will consider three hypotheses that may influence the disparate progression of patellofemoral osteoarthritis (Figure 4). These hypotheses include the duration of the load experienced by the articulating surfaces; the histological, material and compositional properties of the opposing cartilages; and the anabolic/catabolic metabolism of patellar and femoral groove chondrocytes. We propose that these factors interact and perhaps confound one another in the disparate etiology of patellofemoral osteoarthritis (Figure 4).
A schematic depicting three hypotheses considered in this article, their interaction with one another, and influence on the progression of disparate patellofemoral osteoarthritis.
Hypothesis 1: Load Duration
The directly articulating cartilages of the patellofemoral joint experience equal and opposite contact stresses (Newton's third law of action and reaction). Despite an equal magnitude of load, the duration of the loads on a particular area of each surface may differ considerably. For example, one might expect areas of the patellar articular cartilage to be more consistently loaded throughout the range of motion of the knee compared with the intermittent loading of the femoral groove as the patella slides along its length. Intermittent loading may enable fluid flow to flush out waste products and imbibe nutrients that are essential to the maintenance and regeneration of articular cartilage. Static load may reduce this effect, leaving the avascular tissue devoid of nourishment. It is interesting to note that in the 5-yr post-ACLT feline knees exhibiting disparate disease in the patellofemoral compartment, a similar phenomenon was evident in the experimental tibiofemoral compartments. The more consistently loaded tibial plateaus had more severe cartilage damage (full- or partial-thickness erosions) compared with the intermittently loaded femoral condyles (texture changes and only one partial thickness erosion).
In parallel to the work previously described, there is a portion of literature comparing static and dynamic loading of explants of articular cartilage and the effects on the biological response of the tissue. Palmoski and Brandt applied static or dynamic stress to articular cartilage taken from healthy adult dogs. Glycosaminoglycan synthesis was suppressed to 30%-60% of that in controls, and protein synthesis also decreased with static stress. In contrast, when the load was cycled, glycosaminoglycan synthesis was increased by 34%, and there was no effect on protein synthesis. Sah et al. examined the biosynthetic response of calf articular cartilage to dynamic unconfined compression. At high frequencies (0.01-1 Hz), strains of only 1.5% increased 3H-proline and 35S-sulfate incorporation by 20%-40%. In contrast, at low frequencies (0.0001-0.001 Hz), strains less than 5% had no effect. The results from these studies support the notion that static load suppresses the biological response of cartilage, whereas dynamic cyclical load stimulates synthesis. The more consistent loading of the patella compared with the femoral groove may therefore predispose it to impaired biological activity and thus accelerated progression of patellofemoral osteoarthritis.
Hypothesis 2: Histological, Material, and Compositional Properties
In our study of the feline patellofemoral joint, we began with a thorough histological analysis of the cartilage thickness, chondrocyte shape, and chondrocyte volumetric fraction distribution throughout the depth of healthy patellar and femoral groove tissues. We measured these parameters from ruthenium hexamine trichloride/glutaraldehyde-fixed sections taken from the center of the patella or femoral groove. These samples were fixed in situ, still fully intact and attached to their complete native bone under control or loaded (9 MPa) conditions. Nine megapascal was chosen as the average patellofemoral contact pressure measured in situ using Fuji film when 170 N of force was applied across the joint. The peak patellofemoral contact force measured in vivo during normal cat gait is 170 N.
Cartilage Thickness and Strain
We found that patellar cartilage was approximately twice as thick as femoral groove tissue (Figure 2, 5). The extra thickness seemed to be due to an extended deep zone of patellar articular cartilage (Figure 2, 5). For a given load, the femoral groove articular cartilage experienced less strain than the patellar tissue. Furthermore, total tissue strain seemed to be distributed more evenly throughout the layers of the femoral groove compared with the patellar cartilage (Figure 5). The patellar articular cartilage seemed to experience the greatest strains in the middle zone and the smallest strains in the deep zone (Figure 5).
Cartilage depth and compressive strain for healthy feline patellar (pat) and femoral groove (fem) cartilages under control (con) and loaded (9 MPa) conditions. Each bar represents the mean (±SD) depth of samples (n ≥ 4). The superficial, middle, and deep zones are indicated. The percentages overlaid onto loaded samples represent the compressive strain for the entire tissue and the individual zones. Note that the thicker patellar compared with the femoral groove cartilage is largely composed of an extended deep zone. Also, note the smaller and more evenly distributed strains in femoral groove compared with patellar cartilage. [Adapted from Clark, A.L., L.D. Barclay, J.R. Matyas, and W. Herzog. In situ chondrocyte deformation with physiological compression of the feline patellofemoral joint. J. Biomech. 36:553-568, 2003. Copyright © 2003 Elsevier Limited. Used with permission.]
Chondrocyte Aspect Ratio
In both patellar and femoral groove feline cartilages, the cells were organized in a typical zonal arrangement (Figure 2, 6). At the surface, chondrocytes were elliptical in shape and horizontally orientated; the cells in the middle layer were more rounded in shape, and in the deep layer, the cells were elliptical in shape, vertically oriented, and often arranged in columns (P < 0.001). In unloaded samples, the chondrocytes in the superficial zone were more rounded and found within a smaller relative depth of tissue in the patella compared with those in the femur (P < 0.001) (Figure 2, 6). The deep zone columns of cells were also more numerous in the patellar cartilage compared with those in the femoral cartilage. When load was applied to the cartilage, chondrocytes flattened throughout the depth of both femoral and patellar tissues (P < 0.001) (Figure 6). Consistent with total tissue strain, the femoral groove chondrocytes were compressed more uniformly throughout the cartilage depth compared with the patella (Figure 6). Patellar chondrocytes seemed to be compressed more in the upper 40% of the cartilage depth than the femoral chondrocytes. However, in the bottom 40% of the tissue, the patellar chondrocytes seemed to experience similar or less change in aspect ratio than those of the femoral groove.
Healthy feline patellar (pat) and femoral groove (fem) transformed chondrocyte aspect ratio as a function of normalized cartilage depth (0 = surface, 1 = cartilage/bone interface) for control (con) and loaded (9 MPa) groups. Transformed chondrocyte aspect ratio = 3ln(a) + 10, where a is the aspect ratio (height/width) of a chondrocyte. Each point represents the mean (±SD) transformed aspect ratio for chondrocytes (n ≥ 40; n ≥ 4 animals) for a 5% or 10% bin of cartilage depth. Representative ellipses placed at corresponding values of transformed aspect ratio are shown pictorially on the right. Note that femoral groove chondrocytes are flatter and compressed more uniformly throughout cartilage depth compared with patellar chondrocytes. [Adapted from Clark, A.L., L.D. Barclay, J.R. Matyas, and W. Herzog. In situ chondrocyte deformation with physiological compression of the feline patellofemoral joint. J. Biomech. 36:553-568, 2003. Copyright © 2003 Elsevier Limited. Used with permission.]
Chondrocyte Volumetric Fraction
The volumetric fraction of feline chondrocytes was greater in the patellar than in the femoral groove articular cartilage (P < 0.05) and decreased from the superficial zone to the deep layer in both tissues (P < 0.05) (Figure 7). The difference between patellar and femoral cartilage was particularly noticeable in the middle layer where the femoral chondrocyte volumetric fraction was markedly smaller than the corresponding patellar value (Figure 7). Semiquantitative analysis involving measurements of chondrocyte cross-sectional area and visual inspection of morphological sections suggested that this contrast in volumetric fraction was due to both larger and more numerous chondrocytes in the patellar cartilage than in the femoral groove cartilage. Chondrocyte volumetric fraction decreased with load in all layers of both tissues (P < 0.05) (Figure 7). The magnitude of this change was greater in all layers of the patellar cartilage than in those of the femoral cartilage (P < 0.05).
Chondrocyte volumetric fraction as a function of cartilage zone for healthy feline patellar (pat) and femoral groove (fem) cartilage under control (con) and loaded (9 MPa) conditions. Each bar represents the mean (±SD) chondrocyte volumetric fraction for samples (n ≥ 4). Note that chondrocyte volumetric fraction and its decrease under load are larger in patellar compared with femoral groove cartilage. [Adapted from Clark, A.L., L.D. Barclay, J.R. Matyas, and W. Herzog. In situ chondrocyte deformation with physiological compression of the feline patellofemoral joint. J. Biomech. 36:553-568, 2003. Copyright © 2003 Elsevier Limited. Used with permission.]
Material Properties and Biochemical Composition
Other authors have measured the material properties and biochemical composition of the patellofemoral cartilages. Froimson et al. used a needle probe to measure cartilage thickness in the patellofemoral compartment of fresh-frozen healthy human knees. Compressive aggregate modulus, permeability, and Poisson's ratio were also determined for these samples by biphasic indentation testing. Full-thickness cartilage samples adjacent to the indentation sites were taken to measure wet weight, sulfated glycosaminoglycan content, and hydroxyproline content. Numerous significant differences were found between the juxtapose patellofemoral cartilages ( Table 1 ). Patellar cartilage was thicker (P < 0.05) and had a lower compressive aggregate modulus (P < 0.001) and larger permeability to fluid flow (P < 0.001) than the femoral cartilage. The water content of the patella was higher (P < 0.05), and the proteoglycan content was lower (P < 0.05), than that of the femur. No differences were found between the Poisson's ratio and the collagen contents of the tissues ( Table 1 ).
Together, these studies demonstrate structural and compositional differences between the patellar and femoral groove cartilages. Differences exist between unloaded patellar and femoral groove articular cartilage in parameters such as cartilage thickness, chondrocyte shape, and chondrocyte volumetric fraction in both magnitude and depth distribution. Furthermore, under identical applied loads, changes to all of these parameters differ in magnitude and depth distribution between patellar and femoral groove articular cartilage. The patellar is more easily compressed, with a larger water content that is better able to flow out of the tissue during compression, compared with the more proteoglycan-rich femoral groove. These structural and compositional differences between the patellar and femoral groove cartilages may indicate the function of these two surfaces within the patellofemoral joint. The patellar cartilage may play the dominant role in maximizing patellofemoral joint congruence through cartilage deformation during in vivo loading. We hypothesize that the more readily deformed patellar cartilage and chondrocytes may result in predisposing them to altered structural damage and/or biosynthetic activity compared with the femoral groove. One might expect that a larger deformation may create higher localized stresses that could lead to fissuring at the surface of the patellar cartilage close to the edges of contact with the femoral groove. Furthermore, the larger changes in chondrocyte aspect ratio and volumetric fraction may stimulate a more robust metabolic response in the patellar than in the femoral groove chondrocytes.
Hypothesis 3: Chondrocyte Anabolic/Catabolic Metabolism
In situ Messenger Ribonucleic Acid Response to Muscle-Induced Cyclical Load
We recently developed a novel experimental technique to cyclically load intact lapine patellofemoral joints using quadriceps muscle stimulation. The cartilages were cyclically loaded for 2 s every 30 s for 1 h, resulting in an average contact pressure of 4.6 MPa. Cartilage was harvested from central and peripheral regions of the patellar and femoral groove surface, either immediately after loading or after 3 h of recovery. Biological response was assessed on the messenger ribonucleic acid (mRNA) level using reverse transcriptase-polymerase chain reaction (PCR).
RNA concentration (micrograms of RNA per milligram of tissue wet weight) was not significantly influenced by load, location (patella or femoral groove), site (central or peripheral), or harvest time (immediate or 3-h postload). Reverse transcriptase-PCR analysis of RNA from the control and experimental animals revealed that mRNA levels for tissue inhibitor of metalloprotease-1 (TIMP-1), matrix metalloprotease-3 (MMP-3), and basic fibroblast growth factor (bFGF) from the immediate sacrifice group were all significantly affected by the loading protocol. On average, mRNA levels for TIMP-1, MMP-3, and aggrecan were larger in femoral groove compared with those in patellar tissue and vice versa for bFGF and biglycan. Furthermore, tissue from the peripheral harvest sites had significantly greater mRNA levels for decorin compared with that from the central site. In complete contrast, after a 3-h recovery period, neither load nor location had a significant effect on mRNA levels for any of the genes assessed, although harvest site influenced bFGF mRNA levels. Therefore, the rapid disparate changes in mRNA levels immediately after load seemed to be transient. These results support the notion that the opposing cartilage surfaces of the patellofemoral joint respond metabolically to load and are heterogeneous at the cell metabolism level in an in vivo setting.
Proportion of Superficial and Deep Zone Chondrocytes
One of the interesting findings from our histological analyses of the healthy feline patellofemoral joint outlined previously was that the extra thickness of the patellar groove cartilage, compared with femoral groove cartilage, seemed to be the result of an additional depth of deep zone (Figure 2, 5). There is further evidence in the literature supporting differences in the metabolic capacities of chondrocytes isolated from the superficial zone as compared with the deep zone of cartilage.[1,2,19] Deep zone chondrocytes synthesize significantly more proteoglycans and collagens than those from the superficial zone in both explant and isolated chondrocyte culture. In isolated chondrocytes, these differences seem to be retained even after 100-fold expansion. Synthesis and secretion of the superficial-zone protein from superficial zone but not from middle or deep zone chondrocytes has also been reported in both explant and enzymatically digested agarose or alginate cultures. Additionally, superficial and deep zone chondrocytes have been shown to differ in their response to interleukin-1, interleukin-1 receptor antagonist protein, and bone morphogenetic protein (BMP) 2 or BMP-7 overexpression.[4,21] These observations together may suggest that the differing proportions of superficial and deep zone chondrocytes in the patellar and femoral groove cartilages may influence the anabolic and/or catabolic capacity of the tissues, thus predisposing the patellar cartilage to osteoarthritic degeneration as opposed to the femoral groove cartilage.
Summary and Conclusions
Osteoarthritis is a painful and debilitating disease affecting millions of people worldwide. There is presently no cure for this complex disease that can manifest itself in many joints of the body. Studies of knee osteoarthritis have historically focused on the tibiofemoral compartments, with little or no attention being given to the patellofemoral compartment. In this article, patellofemoral osteoarthritis has been highlighted. Patellofemoral osteoarthritis is a common clinical diagnosis associated with disability and often independent of tibiofemoral disease. Furthermore, the manifestation of patellofemoral osteoarthritis across the articulating surfaces of the joint is disparate, the patella demonstrating more severe signs of degeneration at a younger age or shorter time after injury compared with the juxtaposed femoral groove. Investigation into this disparity may hold crucial insights into the etiology of osteoarthritis.
In this article, we have discussed three main hypotheses that may influence this disparity both independently and collectively: load duration; histological, material, and compositional properties; and chondrocyte anabolic/catabolic metabolism (Figure 4). The differences between patellar and femoral groove cartilages and their corresponding chondrocytes are numerous ( Table 2 ). Further consideration of the potential interactions between these properties multiplies the complexity of this "simple" joint. For example, the longer load duration experienced by the patellar cartilage may decrease chondrocyte metabolism relative to the femoral groove. This may be countered, however, by the softer patellar cartilage containing a higher percentage of more metabolically active deep zone chondrocytes. The patellar cartilage will undergo greater deformation than the femoral groove cartilage under a given load, thus resulting in larger aspect ratio and volume changes to patellar chondrocytes and a potentially greater influence on their metabolism. It is clear that even in the simple patellofemoral joint, where cartilage interacts directly with cartilage, the mechanical and metabolic interactions are abundant.
It is interesting to look at these data alongside the body of work by Cole and Kuettner and Kuettner and Cole comparing human cartilages of the ankle and knee. Ankle cartilage is more resistant to progressive degeneration and osteoarthritis than knee cartilage. It is also thinner, stiffer, and less permeable and has a higher proteoglycan content compared with knee cartilage. In addition, ankle chondrocytes synthesize more glycosaminoglycan and protein than knee chondrocytes and up-regulate matrix synthesis as opposed to collagen degradation in response to degeneration. It is interesting that a number of these differences between ankle and knee cartilage match those between femoral groove and patellar cartilage ( Table 2 ). The properties of the more osteoarthritis-resistant ankle and femoral groove cartilages have similar relationships to their counterpart knee and patellar cartilages, respectively.
In conclusion, the patellofemoral compartment of the knee should be considered in addition to the tibiofemoral compartments when diagnosing and investigating knee osteoarthritis. Patellofemoral osteoarthritis is disparate across the joint: the patellar side demonstrating more severe degeneration earlier in the disease process compared with the juxtaposed femoral groove. Duration of the load experienced by the articulating surfaces; the histological, material, and compositional properties of the opposing cartilages; and the anabolic/catabolic metabolism of the chondrocytes from the patellar and femoral groove may all influence the disparate etiology of patellofemoral osteoarthritis.
Table 1. Healthy Human Patellar and Femoral Groove Cartilage Material and Compositional Properties
Table 2. Summary of the Relationship Between Healthy Patellar and Femoral Groove Cartilage for Each Property Discussed in This Article[5,9,13]
This study was supported by a postdoctoral fellowship from the Arthritis Foundation.
Andrea L. Clark, Ph.D., Orthopaedic Research Laboratories, 375 Medical Sciences Research Bldg, Box 3093, Duke University Medical Center, Durham, NC 27710. E-mail: email@example.com .
Andrea L. Clark, Department of Surgery, Division of Orthopaedic Surgery, Orthopaedic Research Laboratories, Duke University Medical Center, Durham, NC