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PubMed2004

Heterogeneous nanomechanical properties of superficial and zonal regions of articular cartilage of the rabbit proximal radius condyle by atomic force microscopy.

Articular chondrocytes have been thought to reside in a homogenous matrix. The physical characteristics of the intercellular matrix of articular cartilage are not well characterized, especially at a nanoscopic scale. The present work tested the hypothesis that the nanomechanical properties of the intercellular matrices of articular cartilage in both the articulating surface and various cellular zones are non-homogeneous. Nanoindentation by atomic force microscopy was applied to the geometric center of the medial, lateral and groove regions of the superficial zone of the rabbit proximal radius cartilage, and then the intercellular matrices of chondrocytes from the superficial to calcifying zones in 40 microm increments. The elastic modulus of the articular surface of the medial condyle (1.46+/-0.11 MPa) was significantly higher than the lateral condyle (1.18+/-0.10 MPa), and the groove (0.96+/-0.07 MPa). There is a significant gradient increase in Young's moduli from the superficial zone (0.52+/-0.05 MPa) to calcifying zone (1.69+/-0.12 MPa). Thus, the nanomechanical properties of the intercellular matrices of the articulating surface are region-specific and likely related to articular function. Heterogeneous biophysical properties of intercellular matrices along the depth from the superficial to calcifying zones suggest that chondrocytes likely reside in a heterogeneous matrix.

Animals↗
PubMed2000

Volumetric changes of articular cartilage during stress relaxation in unconfined compression.

The time-dependent lateral expansion and load relaxation of cartilage cylinders subjected to unconfined compression were simultaneously recorded. These measurements were used to (1) test the assumption of incompressibility for articular cartilage, (2) measure the Poisson's ratio of articular cartilage in compression and (3) investigate the relationship between stress relaxation and volumetric change. Mechanical tests were performed on fetal, calf, and adult humeral head articular cartilage. The instantaneous Poisson's ratio of adult cartilage was 0.49+/-0.08 (mean+S.D.), thus confirming the assumption of incompressibility for this tissue. The instantaneous Poisson's ratio was significantly lower for calf (0. 38+/-0.04) and fetal cartilage (0.36+/-0.04). The equilibrium Poisson's ratio, i.e. true Poisson's ratio of the solid matrix, was significantly higher for the adult tissue (0.26+/-0.11) compared to both the fetal (0.09+/-0.02) and calf (0.11+/-0.03) cartilage. A linear relationship between time-matched load and lateral expansion after the first minute of stress relaxation was observed.

Aging↗
PubMed1999

Influence of radiation synovectomy on articular cartilage, synovial thickness and enhancement as evidenced by MRI in patients with chronic synovitis.

UNLABELLED: Radiation synovectomy is a safe and effective treatment for chronic synovitis that is refractory to the repetitive, intra-articular application of glucocorticosteroids in patients with rheumatoid or seronegative arthritis. Short-term and long-term effects of radiation synovectomy on articular cartilage, synovial enhancement and thickness were assessed in a prospective, clinical trial by MRI. METHODS: Thirteen patients (mean age 39+/-13 y) were treated with a median activity of 8.4 GBq 165Dy ferric hydroxide, a radionuclide with favorable physical properties and a well-documented clinical safety and efficacy profile. MRI was performed on a 1.5-T MR unit using a circular polarized knee coil. RESULTS: After a mean observation period of 13 mo, a marked reduction in synovial enhancement was observed in 10 patients. The mean reduction in baseline synovial thickness (mean 7.6+/-3.0 mm) was 24% (P = 0.03) at 1 wk and 42% (P = 0.01) about 1 y after treatment, respectively. Clinically, 9 of 13 patients (69%) exhibited persistent response to radiation synovectomy. The local clinical score, as defined by the reduction in pain, pannus, joint effusion and by the increase in the range of motion, improved significantly (P = 0.01), from a median of 7 (range 4-10) to a median of 2 (range 0-9). One year after treatment, changes in the local clinical score were related to the decrease in synovial enhancement in MRI (r = 0.7, P = 0.008, n = 12). There were no persistent adverse effects, nor was there evidence for any severe radiation-induced damage to the articular cartilage. On later follow-up images, the structure of the articular cartilage remained unaltered in all but 3 patients, who had new, superficial erosions most likely attributed to an active disease with persistence of inflammation. CONCLUSION: This study suggests that radiation synovectomy with 165Dy-ferric hydroxide is effective in terms of reducing chronic synovitis without causing detectable harm to the articular cartilage, as shown by MRI.

Adult↗
PubMed1984

Zonal analysis of cytoplasmic components of articular cartilage chondrocytes.

The cytoplasmic components of chondrocytes in the various zones of articular cartilage of the medial femoral condyle of adult male New Zealand white rabbits were quantitated from electron micrographs. A progressive increase in the content of endoplasmic reticulum, Golgi apparatus, mitochondria, and electrondense bodies (presumed to be lysosomes) from the tangential zone through the top half of the calcified zone was observed. These organelles then showed a decrease in content in the bottom half of the calcified zone. This was associated with an even greater increase in content of holes in the cytoplasm at that level, providing clear evidence of cellular swelling. Based on these quantitative morphologic studies, it is concluded that the chondrocytes in all zones of articular cartilage are metabolically active, but those cells in the calcified zone show signs of degeneration. The ultimate fate of the chondrocytes in the bottom of the calcified zone is not clear from this study.

Animals↗
PubMed1999

MR evaluation of the articular cartilage of the femoral head during traction. Correlation with resected femoral head.

OBJECTIVE: The purpose was to evaluate the articular cartilage of the hip joint with MR during traction and compare the findings with the resected specimen or arthroscopic findings. MATERIAL AND METHODS: Eight healthy volunteers, 5 patients with osteonecrosis, 5 with acetabular dysplasia, and 5 with advanced osteoarthrosis underwent MR imaging to evaluate the articular cartilage of the hip joint. Coronal fat-suppressed 3D spoiled gradient-echo (SPGR) images were obtained during traction. Identical imaging was performed of all the resected femoral heads of the osteonecrosis and advanced osteoarthrosis patients, and was correlated with the macroscopic pathological findings. RESULTS: The traction was effective and the femoral articular cartilage was clearly identified in all 8 control subjects, and in all cases of osteonecrosis and acetabular dysplasia. In 4 cases of osteonecrosis, chondral fracture was identified in the boundary between the necrosis and the normal area. In all cases of advanced osteoarthrosis, cartilage was identified only at the medial side. The MR images of osteonecrosis and advanced osteoarthrosis corresponded well with the MR images of the resected femoral heads and the macroscopic findings. CONCLUSION: Fat suppressed 3D-SPGR during continuous leg traction was useful in detecting cartilage abnormalities.

Adult↗
PubMed1983

Observations on the senescence of cells derived from articular cartilage.

In the experiments described here, we have sought to determine whether primary cultures of cells derived from articular cartilage will, upon subsequent subculture, undergo in vitro senescence in a manner analogous to that described for several other types of diploid cell. Using cells from the articular cartilage of rabbits, dogs and man, we have established that the population doubling capacity of cultures of these cells is directly related to the specific lifespan of the donor organism. Furthermore, the doubling capacity of the initial cultures of lapine articular chondrocytes is inversely related to the age of the donor rabbit. By these criteria, serially passaged primary cultures of cells derived from articular cartilage appear, a priori, to be a valid system for studies of cellular ageing. Monolayer cultures of lapine chondrocytes appear to "dedifferentiate" after several passages. However, the same cells can be grown as clones, under which conditions they appear to retain better their differentiated properties. Even under these circumstances, lapine articular chondrocytes have a limited capacity for growth, which can be calculated to approximate to the same average number of cell divisions as undergone by monolayer cultures. Lapine chondrocytes frequently transform into established lines of fibroblastic cells. Transformation of canine chondrocytes was more rare, while human chondrocytes have not been observed to transform. This suggests that resistance to transformation is somehow related to lifespan. In addition to furthering our understanding of cellular ageing, studies of the senescence of articular chondrocytes could provide new insights into the aetiology of primary osteoarthritis.

Animals↗
PubMed1986

Purification and characterization of collagenase activator protein synthesized by articular cartilage.

We have isolated an activator of collagenase from medium conditioned with articular cartilage. The activity is contained in an acidic protein appearing as a doublet band of Mr 57,000 and 56,000 on sodium dodecyl sulfate polyacrylamide gels. Both components of the doublet have identical isoelectric points as demonstrated by gel electrophoresis. Purified synovial collagenase has a high dependence on the presence of this factor for activity. Other known activators of latent proteolytic enzymes such as trypsin and mercurials will stimulate collagenase but only if activator protein is present. The activator protein is itself a latent metalloprotease because in the presence of p-aminophenylmercuric acetate and calcium it will digest casein. The caseinase activity and collagenase activation activity have identical heat inactivation profiles, both being stable to a temperature of 60 degrees C and partially inactivated at 80 degrees C. The synthesis of the activator is localized in the superficial zone of articular cartilage.

Animals↗
PubMed1976

[Differences in distribution of type I and type II collagens in the superficial and intermediary zones of articular cartilage].

Undecalcified frozen sections, 40 mu thick, were cut from the knee articular cartilage of young adult Baboons (Papio papio). The sections were freeze dried and the superficial and the intermediate zones were separated by microdissection under a binocular dissecting microscope. The material of each zone was cleaved with CNBr and the major peptides were analyzed by discelectrophoresis in SDS polyacrylamide. Peptides alpha, CB 3,5 and alpha, (II) CB 10 were used as characteristic markers for type I and type II collagen respectively. The method could detect as little as 5-10% of type I collagen of total collagen in mixtures. The thin superficial zone contains type I and type II collagen. The intermediate zone contains only type II collagen. The possible biological significance of this different anatomical distribution of the two types of collagen is discussed. This special distribution could explain the contradictory data from the literature concerning the presence of type I collagen in the articular cartilage.

Animals↗
PubMed2004

Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence.

Senescence compromises the ability of chondrocytes to maintain and repair articular cartilage. We hypothesized that oxidative stress and telomere loss contribute to chondrocyte senescence. To test this hypothesis, we compared the growth of human articular cartilage chondrocytes incubated in 5% O2 and 21% O2. Cells grown in 5% O2 reached 60 population doublings (PD) before senescing, but growth in 21% O2 induced DNA damage and premature senescence at less than 40 PD. Human telomerase reverse transcriptase (hTERT)-transduction failed to prevent chondrocyte senescence in 21% O2, but allowed 1 of 3 chondrocyte strains to exceed 90 PD in 5% O2. These results show that oxidative stress causes premature chondrocyte senescence. They may help explain the increased risk of osteoarthritis with age and after joint trauma and inflammation, and suggest that minimizing oxidative damage will help produce optimal results for chondrocyte transplantation.

Aging↗
PubMed1998

Ageing of equine articular cartilage: structure and composition of aggrecan and decorin.

In order to identify the pathological processes involved in the destruction of articular cartilage in arthritic diseases, it is first necessary to characterise the normal homeostasis of cartilage in a healthy joint. In particular, normal age-related changes in the biochemistry of cartilage complicate any comparisons that are made between diseased and healthy tissue. There are, however, no reports in the literature detailing the influence of ageing on the biochemistry of proteoglycans in equine articular cartilage. This study addresses the absence of such information by investigating the structure of aggrecan and decorin extracted from a wide age-range of full thickness equine tissue. The total glycosaminoglycan content of articular cartilage from the metacarpophalangeal joint remained relatively constant throughout life. In contrast, specific components such as hyaluronan increased in concentration with advancing age as did the content of a structural epitope present on keratan sulphate chains. There were also significant age-related changes in the sulphation pattern of chondroitin sulphate chains. The structure of the large aggregating proteoglycan (aggrecan) became more heterogeneous in size with increasing age and each of the subspecies of aggrecan identified in the extracts was shown to carry a hyaluronan binding region (G1) domain. All subspecies of aggrecan also expressed specific epitopes to keratan sulphate, chondroitin-4-sulphate and chondroitin-6-sulphate glycosaminoglycan chains. The structure of the small nonaggregating proteoglycan decorin and the aggrecan stabilising molecule link protein were demonstrated to be similar in size and charge to that reported for other species.

Aggrecans↗
PubMed1993

Characterization of proteoglycans isolated from associative extracts of human articular cartilage.

Approx. 10% of the total proteoglycan content of normal young human articular cartilage was extracted under associative conditions with Dulbecco's PBS. Proteoglycans isolated from the extract by Q-Sepharose chromatography were separated by gel chromatography and characterized by gradient gel SDS/PAGE and immunoblotting. Three species of small proteoglycans, two main populations of aggrecan and a population of its smaller fragments were identified. The major populations of aggrecan contained chondroitin sulphate chains, all or part of the N-terminal G1 and G2 domains and, therefore, intact keratan sulphate domains. The larger population was estimated by gradient SDS/PAGE to have a molecular mass of approx. 600 kDa or greater. The second population had an apparent molecular mass of approx. 300-600 kDa. Core proteins derived from these populations of proteoglycans separated on SDS/PAGE into several clusters of bands in the range from 120 to approx. 360 kDa. The extract further contained smaller fragments which lacked chondroitin sulphate but reacted with antibodies against keratan sulphate, and against epitopes present in the G2 domain of aggrecan. The presence of the G2 domain in a broad range of populations of decreasing size indicated extensive cleavage of the aggrecan core protein within its chondroitin sulphate domain. These findings suggest that fragmentation of aggrecan probably occurs in vivo in normal articular cartilage of young individuals. Associative extracts also contained decorin, biglycan and fibromodulin. These were resolved from aggrecan by gel chromatography and identified by immunodetection.

Aggrecans↗
PubMed2003

Effect of NOS2 gene deficiency on the development of autoantibody mediated arthritis and subsequent articular cartilage degeneration.

OBJECTIVE: To determine the effect of NOS2 gene deletion on articular cartilage degradation in autoantibody mediated arthritis (AMA). METHODS: Female C57BL/6Ai-[ko] NOS2 N5 (NOS2-/-) mice (7-8 weeks old) and the counterpart C57/Bl6 Crj mice (wild-type, WT) were studied. Arthritis was induced by intraperitoneal injection of 4 mg of an arthritogenic cocktail of 4 monoclonal antibodies raised against type II collagen twice on Day 0 and Day 1 followed by intraperitoneal injection of 50 micro g of lipopolysaccharide on Day 2. Individual limbs were scored for arthritis in 4 grades; the total maximum score per mouse was 16. Femoral condyles and tibial plateaus of both knee joints were collected on Day 15 for immunohistological studies on nitrotyrosine and matrix metalloproteinase (MMP)-3 and -9. DNA fragmentation in chondrocytes was detected by the nick-end labeling (TUNEL) method. Blood was also collected on Day 15 to determine serum levels of nitrite/nitrate and interleukin 1 beta (IL-1 beta). RESULTS: Both NOS2-/- and WT mice with AMA developed clinically apparent arthritis. In WT mice, the arthritis progressed rapidly and reached the peak score 11.4 +/- 2.9 on Day 12, whereas the arthritis in NOS2-/- mice was milder and the peak score was 7.7 +/- 2.8 on Day 13 (p < 0.05). The serum nitrite/nitrate levels, histological grades of articular cartilage degradation, and numbers of apoptotic chondrocytes and nitrotyrosine positive chondrocytes were significantly lower in NOS2-/- mice with AMA than in WT mice with AMA. Conversely, significant differences were not observed in MMP-3 or -9 expression in chondrocytes, or in serum IL-1 beta levels between these 2 groups of mice. CONCLUSION: NOS2 gene deletion did not affect the inflammatory responses, but reduced the cartilage degradation.

Animals↗
PubMed1987

Morphological studies on the articular cartilage of old rats.

Age-dependent morphological alterations of the tibial articular cartilage were studied in 26-month-old Wistar rats of both sexes. Young and adult rats (6 and 10 months of age, respectively) served as a basis for comparison. Light microscopic histology, polarization optical analysis (toluidine-blue staining with or without the addition of 0.2, 0.4 or 0.8 M MgCl2, as well as after phenol reaction) as well as transmission electron microscopy were applied. The main observations are: (1) According to the histological findings, the proportion of the zones changes with age; the subchondral bone layer becomes wider and separated to a certain extent, while the fibres become demasked. (2) Polarization microscopy revealed a disorientation of both the proteoglycane (PG) and collagen molecules; considering the available biochemical data, this phenomenon involves both quantitative and structural changes, as well as differences in the localization of the PG and collagen molecules. (3) Electron microscopy also supports the structural alterations of the collagen (thin and thick, as well as non-striated, fragmented fibres). Cellular alterations are also observed parallel with the changes of the matrix (cell organelles occur less frequently, signs of degeneration and disintegration, rupture of the plasma membrane, as well as accumulation of lipid-bodies can be seen. On the basis of the findings, one can consider the articular cartilage in the old rats as a tissue which is still in equilibrium, however, aged chondrocytes with decreased function become predominant in it. This state can be modified into a pathological one by various mechanical, endocrinological, iatrogenic, post-traumatic, etc., influences through the alterations of the cell-matrix interactions.

Aging↗
PubMed2000

Functional estrogen receptors in adult articular cartilage: estrogen replacement therapy increases chondrocyte synthesis of proteoglycans and insulin-like growth factor binding protein 2.

OBJECTIVE: Epidemiologic studies suggest a protective effect of estrogen replacement therapy (ERT) against the development of knee and hip osteoarthritis, but a potential mechanism for this effect is not known. The present study was done to determine if functional estrogen receptors (ERs) are present in adult articular cartilage and to determine if ERT in vivo affects the production of insulin-like growth factor binding proteins (IGFBPs). METHODS: Reverse transcription-polymerase chain reaction, immunoblotting, and immunohistochemistry were used to measure messenger RNA (mRNA) and protein for ERs in adult monkey articular cartilage. Cultured chondrocytes transfected with a reporter construct containing the estrogen response element (ERE/luciferase) were stimulated with estrogen in vitro to determine functional activity of the ERs. IGFBP production was measured by ligand and immunoblotting of conditioned media of cells cultured from control and estrogen-treated surgically menopausal monkeys. Proteoglycan (PG) synthesis was estimated by measurement of 35SO4 incorporation. RESULTS: ERa and ERbeta mRNA were present in adult monkey articular cartilage, and ER protein was demonstrated by immunoblotting and immunohistochemistry. Estrogen treatment in vitro of cells transfected with the ERE/luciferase construct resulted in a 2.87-fold increase (P = 0.0163) in reporter production over that of untreated cells. Compared with untreated controls, IGFBP-2 production was significantly increased (P < 0.008) in conditioned media of chondrocytes cultured from monkeys that had received ERT in vivo. Increased IGFBP-2 in these cultures was associated with a 1.41-fold increase (P = 0.02) in the level of sulfate incorporation. CONCLUSION: Transcriptionally functional ER are present in adult articular cartilage, and ERT increases the production of IGFBP-2 and the synthesis of PGs by chondrocytes from surgically menopausal monkeys. These results indicate that estrogen can have a direct effect on adult articular cartilage.

Adult↗
PubMed1992

[Undesirable effects of drying on articular cartilage].

Knee joints of mature rabbit were exposed to room air (room temperature 23 degrees C, humidity 63.5%) for a period ranging from 30 minutes to hours to imitate the human situation in operating room. The morphological findings indicated that the articular cartilage of the femur trochlea was moderately degenerated after 30 minutes of drying and obvious degeneration occurred two hours after operation. The articular cartilage of the patella also degenerated after two-hour drying. No necrosis was noted in the cartilage of the femoro-tibial joint as that part could not be exposed thoroughly. It was possible to reduce the degenerative changes of articular cartilage if the joint was irrigated with Ringer's solution every 5 minutes. The results indicated that drying, a physical factor, can induce the degeneration of the articular cartilage. The longer the drying time, the more obvious the degenerative changes of cartilage; Ringer's solution is useful to prevent the degenerative changes. Clinically, the following points are worth considering: (1) Operating under arthroscope is much better than arthrotomy in avoiding the degenerative change of the cartilage; (2) The operating time should be as short as possible; (3) It is useful to irrigate the joint with some liquid to keep the joint surface moist; and (4) The consequence of exposure of the joint cartilage in cases of open injury of the joint must be seriously considered.

Air↗
PubMed1995

A theoretical solution for the frictionless rolling contact of cylindrical biphasic articular cartilage layers.

Previous studies have shown that interstitial fluid pressurization plays an important role in the load support mechanism of articular cartilage under normal step loading. These studies have demonstrated that interstitial fluid pressurization decreases with time if the applied load is maintained constant. In the present study, a theoretical solution is obtained for another common loading of articular cartilage, namely the contact of surfaces in rolling motion. Pure rolling of symmetrical frictionless cylindrical cartilage layers is analyzed under steady state. The linear biphasic model of Mow et al. [J. Biomech. Engng 102, 73-84 (1980)] is used to describe the mechanical response of articular cartilage. The solution of this contact problem reduces to simultaneously solving a set of four integral equations, akin to the dual integral problem of elastic contact. It is found that the solution is dependent on four non-dimensional parameters: Rh = Vb/HAk, W/2 mu b, R/b, and v, where V is the surface velocity, b the cartilage thickness, HA the aggregate modulus, mu the shear modulus, v Poisson's ratio, k the permeability, R the radius of cylindrical surfaces, and W the applied load per unit cylinder length. For Rh << 1, interstitial fluid pressurization is found to be negligible, and all the applied load is supported by the solid collagen-proteoglycan phase of the tissue, thus causing significant cartilage deformation. As Rh increases to a physiological level (Rh approximately 10(4)), interstitial fluid pressurization may support more than 90% of the total applied load, shielding the solid matrix from high effective stresses and reducing matrix strains and deformation. The protective effect of interstitial fluid pressurization is observed to increase with increasing joint congruence (R/b); similarly, as the applied load (W/2 mu b) is increased, a greater proportion of it is supported by the fluid. In degenerative cartilage, Rh may drop by one or more orders of magnitude, primarily as a result of increased permeability. Thus, the protective stress-shielding effect of interstitial fluid pressurization may become less effective in diseased tissue, possibly setting a pathway for further tissue degeneration.

Algorithms↗
PubMed2003

The role of cell seeding density and nutrient supply for articular cartilage tissue engineering with deformational loading.

OBJECTIVE: Functional tissue engineering (FTE) of articular cartilage involves the use of physiologically relevant mechanical signals to encourage the growth of engineered constructs. The goal of this study was to determine the utility of deformational loading in enhancing the mechanical properties of chondrocyte-seeded agarose hydrogels, and to investigate the role of initial cell seeding density and nutrient supply in this process. DESIGN: Chondrocyte-seeded agarose hydrogels were cultured in free-swelling conditions or with intermittent deformational loading (10% deformation, 1 Hz, 1 h on/ 1 h off, 3 h per day, five days per week) over a two-month culture period. Disks were seeded at lower (10 million cells/ml) and higher (60 million cells/ml) seeding densities in the context of a greater medium supply than previous studies (decreasing the number of cells/ml feed medium/day) and with an increasing concentration of fetal bovine serum (10 or 20% FBS). RESULTS: Under these more optimal nutrient conditions, at higher seeding densities and high serum concentration (20% FBS), dynamically loaded constructs show >2-fold increases in material properties relative to free-swelling controls. After two months of culture, dynamically loaded constructs achieved a Young's modulus of approximately 185 kPa and a dynamic modulus (at 1 Hz) of approximately 1.6 MPa, with a frequency dependent response similar to that of the native tissue. These values represent approximately 3/4 and approximately 1/4 the values measured for the native tissue, respectively. While significant differences were found in mechanical properties, staining and bulk measurements of both proteoglycan and collagen content of higher seeding density constructs revealed no significant differences between free-swelling and loading groups. This finding indicates that deformational loading may act to increase material properties via differences in the structural organization, the production of small linker ECM molecules, or by modulating the size of macromolecular proteoglycan aggregates. CONCLUSIONS: Taken together, these results point to the utility of dynamic deformational loading in the mechanical preconditioning of engineered articular cartilage constructs and the necessity for increasing feed media volume and serum supplementation with increasing cell seeding densities.

Animals↗
PubMed1987

Electron microscopic analysis of articular cartilage proteoglycan degradation by growth plate enzymes.

To assess the effect of intracellular growth plate chondrocyte enzymes on proteoglycan structure, we examined enzyme-treated articular cartilage proteoglycans and untreated articular cartilage proteoglycans with the electron microscopic monolayer technique. The untreated proteoglycan monomers ranged in length from less than 20 nm to more than 700 nm, with a mean length of 224.5 +/- 101.6 nm in one experiment and 224.6 +/- 95.7 nm in a second experiment. Incubation with growth plate enzymes reduced proteoglycan monomers to fragments with lengths that varied from less than 5 nm to 143 nm, increased the variability in monomer length, and destroyed proteoglycan aggregates. The enzyme treated monomers had an average length of 29.5 +/- 17.9 nm in one experiment and 35.2 +/- 17.0 nm in a second experiment. The smallest common fragments were 15 nm long and would be expected to contain about 15 glycosaminoglycan chains. This experiment demonstrates that enzymes extracted from growth plate chondrocytes can degrade the chondroitin sulfate-rich region of proteoglycan monomer core proteins, produce a range of monomer fragment sizes with less than 2% of the fragments shorter than 5 nm or longer than 100 nm, increase the variability in monomer length, and degrade proteoglycan aggregates.

Animals↗