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Early diagnosis and treatment of pre- and early-stage osteoarthritis (OA) is important. However, the cellular and cartilaginous changes occurring during these stages remain unclear. We investigated the histological and immunohistochemical changes over time between pre- and early-stage OA in a rat model of traumatic injury. Thirty-six male rats were divided into two groups, control and OA groups, based on destabilization of the medial meniscus. Histological and immunohistochemical analyses of articular cartilage were performed on days 1, 3, 7, 10, and 14 postoperatively. Cell density of proteins associated with cartilage degradation increased from postoperative day one. On postoperative day three, histological changes, including chondrocyte death, reduced matrix staining, and superficial fibrillation, were observed. Simultaneously, a compensatory increase in matrix staining was observed. The Osteoarthritis Research Society International score increased from postoperative day seven, indicating thinner cartilage. On postoperative day 10, the positive cell density decreased, whereas histological changes progressed with fissuring and matrix loss. The proteoglycan 4-positive cell density increased on postoperative day seven. These findings will help establish an experimental model and clarify the mechanism of the onset and progression of pre- and early-stage traumatic OA., (© 2024. The Author(s).)

Objective: The study aim was to evaluate the histological relationship between osteoarthritis (OA) and articular cartilage in disuse atrophy induced by hindlimb unloading in a post-traumatic OA rat model., Design: Forty male rats were divided into the 4 following experimental groups: control, hindlimb suspension (HS), OA induced by destabilization of the medial meniscus (OA), and OA induction after hindlimb suspension (HS-OA). Histological changes in the articular cartilage of the tibia were evaluated by the Osteoarthritis Research Society International (OARSI) scores and histomorphometrical analyses at 2, 4, and 8 weeks after OA induction., Results: We confirmed that disuse atrophy of the articular cartilage was caused by thinning of the articular cartilage and the decrease in matrix staining for the nonloading period of 4 weeks. The OARSI scores and histomorphological analyses revealed that OA progressed significantly wider and deeper in the HS-OA group than in the OA group over time. In the sham group, disuse atrophy of the articular cartilage recovered at 2 weeks after reloading., Conclusions: This study revealed that OA progressed faster in cartilage atrophy than in normal articular cartilage. Further studies are required for investigating the mechanisms of disuse atrophy of cartilage and its association with OA using the biochemical and immunohistochemical analysis.

Objective: Curcumin monoglucuronide (TBP1901) is highly water soluble and can convert to free form curcumin, which has pharmacological effects, on intravenous administration. This study aimed to investigate the effectiveness of TBP1901 intra-articular injections in an osteoarthritis (OA) rat model., Methods: Sixty-four male Wistar rats (12 weeks old) who underwent destabilized medial meniscus (DMM) surgery were randomly separated into the TBP1901 injection or saline solution (control) injection group. They were sacrificed at 1, 2, 6, or 10 weeks postoperatively (weeks 1, 2, 6, and 10; n = 8 for each group). TBP1901 (30 mg/mL) or saline solution of 50 μL was injected into the knee joints twice a week during weeks 1 and 2 to investigate the effects in the acute phase of posttraumatic (PT) OA or once a week during weeks 6 and 10 to investigate it in the chronic phase of PTOA. Histology, immunohistochemistry, and micro-computed tomography were performed to evaluate the changes in OA., Results: TBP1901 injections significantly reduced synovial inflammation at weeks 1 and 2, and tumor necrosis factor-α expression in the articular cartilage at week 6. The TBP1901 injections also significantly suppressed articular cartilage damage, subchondral bone (SB) plate thickening, SB plate perforation, and osteophyte formation at week 10., Conclusions: TBP1901 intra-articular injections suppressed synovial inflammation in the acute phase of PTOA in DMM rats. In the chronic phase, TBP1901 suppresses articular cartilage damage and regulates SB plate changes.

The pathophysiology of primary osteoarthritis (OA) remains unclear. However, a specific subclassification of OA in relatively younger age groups is likely correlated with a history of articular cartilage damage and ligament avulsion. Surgical animal models of OA of the knee play an important role in understanding the onset and progression of post-traumatic OA and aid in the development of novel therapies for this disease. However, non-surgical models have been recently considered to avoid traumatic inflammation that could affect the evaluation of the intervention. In this study, an intra-articular cartilage lesion rat model induced by in vivo cyclic compressive loading was developed, which allowed researchers to (1) determine the optimal magnitude, speed, and duration of load that could cause focal cartilage damage; (2) assess post-traumatic spatiotemporal pathological changes in chondrocyte vitality; and (3) evaluate the histological expression of destructive or protective molecules that are involved in the adaptation and repair mechanisms against joint compressive loads. This report describes the experimental protocol for this novel cartilage lesion in a rat model.

Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA.

This study aimed to investigate the histopathological changes in the patellofemoral joint using a rat model of osteoarthritis that was induced using monosodium iodoacetate, and to establish a novel model of patellofemoral osteoarthritis in a rat model using histopathological analysis. Sixty male rats were used. Osteoarthritis was induced through a single intra-articular injection of monosodium iodoacetate in both knee joints. Animals were equally divided into two experimental groups based on the monosodium iodoacetate dose: 0.2 mg and 1.0 mg. Histopathological changes in the articular cartilage of the patellofemoral joint and the infrapatellar fat pad were examined at 3 days, 1 week, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the monosodium iodoacetate injection. In the 1.0-mg group, the representative histopathological findings of osteoarthritis were observed in the articular cartilage of the patellofemoral joint over time. Additionally, the Osteoarthritis Research Society International scores of the patellofemoral joint increased over time. The synovitis scores of the infrapatellar fat pad in both groups were highest at 3 days, and then the values decreased over time. The fibrosis score of the infrapatellar fat pad in the 1.0-mg group increased with time, whereas the fibrosis score in the 0.2-mg group remained low. Representative histopathological findings of osteoarthritis were observed in the articular cartilage of the patellofemoral joint in a rat model of osteoarthritis induced using monosodium iodoacetate. With appropriate selection, this model may be regarded as an ideal patellofemoral osteoarthritis model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

ABSTRACT This cross-sectional study examined the relationship of flat feet with knee pain, disability, and physical performance in patients with knee osteoarthritis (OA). Orthopedic clinic participants ( n = 95; age 61-91 years; 68.4% women) with Kellgren-Lawrence (K/L) grade ≥1 in the medial compartment underwent evaluation of navicular height and foot length for flat feet. Knee pain intensity, disability, and physical performance were evaluated using the Japanese Knee Osteoarthritis Measure, 10-m walk, timed up and go, and five-repetition chair stand tests. Of the 95 enrolled patients, 24 (25.3%) had bilateral flat feet, and significantly higher knee pain compared to patients with no flat feet (11.3 ± 8.23 points vs. 6.58 ± 6.37 points; p = 0.043). A ordinal logistic regression analysis showed that bilateral flat feet were significantly associated with increased knee pain (proportional odds ratio: 5.48, 95% confidence interval: 1.96, 15.3; p = 0.001) compared with no flat feet, adjusted for age, sex, body mass index, and tibiofemoral joint K/L grade, which is consistent across various different cutoffs of the definition of flat feet. Physical performance was similar between patients with and without bilateral flat feet. The presence of unilateral flat feet was not significantly associated with any outcome measures. These findings indicate that bilateral, but not unilateral, flat feet are associated with worse knee pain. A prospective study investigating a causal relationship between bilateral flat feet posture and knee pain as well as disability would be of particular interest to verify the potential adverse effect of altered foot posture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2490-2498, 2017. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical impact in knee osteoarthritis (OA) of coexisting patellofemoral (PF) joint OA (PFOA) in Japanese patients with medial tibiofemoral (TF) joint OA (TFOA).Methods: Patients with medial knee OA (n = 143) were enrolled. The radiographic severity of the TF and PF joints, anatomic axis angle of the TF joint, patellar alignment, trochlear morphology, patellar height, and passive range of motion (ROM) of the painful knee were evaluated. Additionally, the Japanese Knee Osteoarthritis Measure (JKOM) was used to investigate the association between the presence of PFOA and clinical symptoms.Results: PFOA was present in 98 of 143 patients (68.5%) with medial knee OA. Quantile regression analysis revealed that coexisting PFOA was associated with the pain-related subcategory of the JKOM. Furthermore, multiple logistic regression analysis showed that coexisting PFOA was associated with higher odds of reporting knee pain on using stairs while ascending (odds ratio [OR] 4.81 [95% confidence interval (95% CI) 1.73, 14.3]) and descending (OR 3.86 [95% CI 1.44, 10.8]). A more varus knee alignment and lower knee flexion ROM, which are features of patients with coexisting PFOA, were associated with knee pain while ascending/descending stairs. However, patellar alignment, trochlear morphology, and patellar height were not significantly associated with knee pain.Conclusion: PFOA coexisting with medial knee OA was associated with worse clinical symptoms, particularly while ascending/descending stairs, although patellar alignment did not contribute to reporting knee pain. Further studies that include evaluation of the PF joint are warranted to develop a basis for an optimal intervention based on compartmental involvement. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods. Patients in an orthopedic clinic (n5266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n5173), dynamic varus (n517), static varus (n550), and static varus1dynamic varus (n526).The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results. Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08-12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19- 320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion. Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. [ABSTRACT FROM AUTHOR]

Recognizing subtle cartilage changes in the preclinical stage of osteoarthritis (OA) is essential for early diagnosis. To this end, the ability of the ultrasound signal intensity to detect macroscopically undetectable cartilage change was investigated. In this study, cartilage of rabbit OA model and human OA samples was examined by macroscopic evaluation, ultrasound signal intensity, histology with Mankin scores, and Fourier transform infrared imaging (FTIRI) analysis. Rabbit OA was induced by anterior cruciate ligament transection and evaluated at 1, 2, 4 and 12 weeks. Twenty human samples were harvested during total knee arthroplasty from OA patients who had macroscopically normal human cartilage (ICRS grade 0) on the lateral femoral condyle. In the animal study, there was no macroscopic OA change at 2 weeks, but histology detected degenerative changes at this time point. Ultrasound signal intensity also detected degeneration at 2 weeks. In human samples, all samples were obtained from macroscopically intact site, however nearly normal (0≤ Mankin score <2), early OA (2≤ Mankin score <6), and moderate OA (6≤ Mankin score <10) samples were actually intermixed. Ultrasound signal intensity was significantly different among these 3 stages and was well correlated with Mankin scores (R = −0.80) and FTIR parameters related to collagen and proteoglycan content in superficial zone. In conclusion, ultrasound can detect microscopic cartilage deterioration when such changes do not exist macroscopically, reflecting superficial histological and biochemical changes. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to elucidate whether the levels of serum biomarkers reflect the progression of osteoarthritis (OA) induced by different levels of exercise. Thirty-five Wistar rats subjected to anterior cruciate ligament transaction (ACLT) were divided into three groups: Control, moderate running, and intense running. Twelve rats (moderate running without ACLT) were allocated as a naive group. Running was performed on a motorized treadmill, at a speed of 18 m/min for 30 min/day (moderate and naive) or 60 min/day (intense) for 3 days per week. After 2 or 4 weeks, OA histopathology in the knees was evaluated using the Osteoarthritis Research Society International (OARSI) score, and the serum levels of cleaved collagen type II (C2C) and procollagen II C-propeptide (CPII) were analyzed. The OARSI score deteriorated in the intense running group after 2 weeks and the serum C2C/CPII ratio suggested the development of OA. At 4 weeks, the C2C/CPII ratio suggested there would be deterioration in the OARSI score but the score did not differ significantly between the moderate and intense running groups. C2C/CPII ratio had 13-25% correlation with the OARSI histological score. Thus, in rat experimental OA, the OARSI score could be partially predicted by the C2C/CPII ratio as a serum biomarker of OA. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1026-1031, 2013 [ABSTRACT FROM AUTHOR]

Objective: This study aimed to clarify the effects of periodic mild heat stimuli on extracellular matrix (ECM) synthesis of adult human chondrocytes in 3-dimensional pellet culture. Results: Human articular chondrocytes were subjected to pellet culture at 37 °C for 3 days. Thereafter, the pellets were divided into three groups: 32 °C group which was cultured at 32 °C without heat stimuli, 32 °C + Heat group which was cultured at 32 °C and applied periodic heat stimuli, 37 °C group which was cultured at 37 °C. Heat stimuli were given by transferring the pellets into a CO2 incubator set at 41 °C for 20 min/day, 6 times/week. ECM synthesis ability was evaluated by analyzing the mRNA expressions. Additionally, the collagen and proteoglycan content in the pellet was quantified. DNA content was also measured for estimating the cell amount. We found that there were no significant differences in the mRNA expression of COL2A1, COL1A1, and ACAN between the 32 °C group and 32 °C + Heat group. However, the collagen content per cell and DNA content were significantly lower in the 32 °C + Heat group compared to other groups. Our results indicate that periodic mild heat stimuli may diminish ECM synthesis due to inhibition of collagen production and loss of cells. [ABSTRACT FROM AUTHOR]

This systematic review with a meta-analysis aimed to summarize the current evidence of the effectiveness of mesenchymal stem cell (MSC) treatment for knee osteoarthritis (OA) and to examine whether rehabilitation is an effect modifier of the effect estimate of MSC treatment. A literature search yielded 659 studies, of which 35 studies met the inclusion criteria (n = 2385 patients; mean age: 36.0–74.5 years). The meta-analysis results suggested that MSC treatment through intra-articular injection or arthroscopic implantation significantly improved knee pain (standardized mean difference [SMD]: −1.45, 95% confidence interval [CI]: −1.94, −0.96), self-reported physical function (SMD: 1.50, 95% CI: 1.09, 1.92), and cartilage quality (SMD: −1.99; 95% CI: −3.51, −0.47). However, the MSC treatment efficacy on cartilage volume was limited (SMD: 0.49; 95% CI: −0.19, 1.16). Minor adverse events (knee pain or swelling) were reported with a wide-ranging prevalence of 2–60%; however, no severe adverse events occurred. The evidence for these outcomes was "very low" to "low" according to the Grades of Recommendation, Assessment, Development and Evaluation system because of the poor study design, high risk of bias, large heterogeneity, and wide 95% CI of the effects estimate. Performing rehabilitation was significantly associated with better SMD for self-reported physical function (regression coefficient: 0.881, 95% CI: 0.049, 1.712; P = 0.039). We suggest that more high quality randomized controlled trials with consideration of the potential rehabilitation-driven clinical benefit would be needed to facilitate the foundation of effective MSC treatment and regenerative rehabilitation for patients with knee OA. [ABSTRACT FROM AUTHOR]

Objective To examine the association between pedometer-based ambulatory physical activity (PA) and physical function in patients with knee osteoarthritis (OA). Design Cross-sectional observational study. Setting Institutional practice. Participants Participants in orthopedic clinics (N=207; age, 56–90y; 71.5% women) with diagnosed radiographic knee OA (Kellgren/Lawrence [K/L] grade ≥1). Interventions Not applicable. Main Outcome Measures Ambulatory PA was objectively measured as steps per day. Physical function was assessed using the Japanese Knee Osteoarthritis Measure (JKOM) functional subcategory, 10-m walk, Timed Up and Go (TUG), and 5-repetition chair stand (5CS) tests. Results Patients walking <2500 steps/d had a low level of physical function with a slower gait speed, longer TUG time, and worse JKOM functional score compared with those who walk 2500 to 4999, 5000 to 7499, and ≥7500 steps/d adjusted for age, sex, body mass index [BMI], and K/L grade. Ordinal logistic regression analysis revealed that steps per day (continuous) was associated with better physical function adjusted for age, sex, BMI, and K/L grade. These relationships were still robust in sensitivity analyses that included patients with K/L grades ≥2 (n=140). Conclusions Although increased ambulatory PA had a positive relationship with better physical function, walking <2500 steps/d may be a simple indicator for a decrease in physical function in patients with knee OA among standard PA categories. Our findings might be a basis for counseling patients with knee OA about their ambulatory PA and for developing better strategies for improving physical function in sedentary patients with knee OA. [ABSTRACT FROM AUTHOR]

Background: Cartilage and subchondral bone have recently been considered an osteochondral unit. The treatment of osteo-chondral lesions is still challenging, but better subchondral bone repair may result in higher quality repaired cartilage.Hypotheses: Alendronate accelerates bone formation in osteochondral defects and affects the quality of the repaired cartilage.Study Design: Controlled laboratory study.Methods: Osteochondral defects were made on the left trochleas of 50 rabbits, which were assigned to 1 of 3 groups: control, ALN (weekly subcutaneous injection of 0.14 mg/mL alendronate), and ALN-S (alendronate injection in the first 8 weeks only). They were evaluated at 4, 8, 24, and 52 weeks. Bone repair was evaluated with microcomputed tomography and histologic evaluation. Cartilage repair was evaluated with ultrasound and histologic analyses.Results: At 4 weeks, the defects were filled, and cartilage-like repair tissue was observed in the ALN group, whereas the defects were incompletely filled in the control group. Alendronate treatment enhanced early bone formation and mineralization in the osteochondral defect for the first 8 weeks. The continuous injection of alendronate for 24 weeks resulted in delayed bone remodeling, but the rabbits in the ALN-S group showed good integrity of the subchondral bone plate, without delayed remodeling. At 52 weeks, the ALN-S group had a columnar arrangement of chondrocytes that had less fibrillation and looked superior to those in the ALN and control groups. Ultrasound analysis showed better quality of repaired cartilage of the ALN and ALN-S group than the control group.Conclusion: Alendronate accelerated bone formation without inhibiting its mineralization but thereafter inhibited bone remodeling in an osteochondral defect. The withdrawal of alendronate at 8 weeks avoided the delayed remodeling and showed better sub-chondral bone repair. At 52 weeks, better subchondral bone repair resulted in better cartilage quality.Clinical Relevance: Alendronate administered in the early period accelerates bone formation and improves the quality of the repaired cartilage. [ABSTRACT FROM PUBLISHER]

This study was aimed at investigating the use of ultrasound parameters obtained non-invasively through soft tissue (ST) to evaluate degeneration in cartilage and subchondral bone (SB) in the human knee. We developed a 3-D ultrasound system and introduced the ratio parameters Rcb and RcbT to suppress the attenuation effect in the ST or in both the ST and cartilage. As reference measurements, the grade for cartilage by visual judgment (Gsum) and ultrasound parameters for the cartilage and the SB were directly evaluated under arthroscopy. Rcb correlated significantly with Gsum (rs = -0.63) and with the corresponding parameter obtained directly under arthroscopy (r = 0.55). RcbT also correlated significantly with Gsum (rs = -0.46) but was not superior to Rcb. Rcb is considered to be an efficient parameter that reflects the total degeneration in both the cartilage and SB, including the information on cartilage thickness. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify ultrasound parameters reflecting subchondral porosity (Po), subchondral plate thickness (Tpl) and bone volume fraction at the trabecular bone region (BV/TVTb). Sixteen osteoarthritic human lateral femoral condyles were evaluated ex vivo using a 15-MHz pulsed-echo ultrasound 3-D scanning system. The cartilage-subchondral bone (C-B) surface region (layer 1) and inner subchondral bone region (layer 2) were analyzed; we newly introduced entropy (ENT) and correlation (COR) of ultrasound texture parameters of the parallel (x) or perpendicular (z) direction to the C-B interface for this analysis. Po, Tpl and BV/TVTb were evaluated as reference measurements using micro-computed tomography. ENTL1x (ENT of layer 1, x-direction) and ENTL1z were significantly correlated with Po (both r values = 0.58), CORL2x with Tpl (r = -0.73) and CORL2z with BV/TVTb (r = -0.66). These are efficient indicators of the characteristics of osteoarthritis-related subchondral bone; the other texture parameters were not significant. [ABSTRACT FROM AUTHOR]

This cross-sectional study investigated (i) the association of varus thrust during gait with the presence of patellofemoral osteoarthritis (PFOA) in patients with medial knee osteoarthritis (OA) and (ii) patellar alignment in the knees with varus thrust. Participants from orthopedic clinics (n=171; mean age, 73.4 years; 71.9% female) diagnosed with radiographic medial knee OA (Kellgren/Lawrence [K/L] grade ≥1) were included in this study, and underwent gait observation for varus thrust assessment using 2D video analysis. A radiographic skyline view was used to assess the presence of medial PFOA using the grading system from the Osteoarthritis Research Society International Atlas. The tibiofemoral joint K/L grade, patellar alignment (i.e., lateral shift and tilting angle), and knee pain intensity were also evaluated as covariates. Thirty-two (18.7%) of 171 patients exhibited varus thrust and they presented significantly higher knee pain (46.0±3.04mm vs. 32.4±2.73mm; P=0.024), a lower patellar tilting angle (P=0.024), and a higher prevalence of PFOA compared with those without varus thrust. A logistic regression analysis with adjustment of covariates showed that varus thrust was significantly associated with higher odds of the presence of mixed and medial PFOA, and trended to significantly associate with any PFOA, including lateral PFOA. This indicates that varus thrust was associated with PFOA in a compartment-nonspecific manner in patients with medial knee OA. Varus thrust may represent a clinical disease feature of more advanced and multicompartmental disease. [ABSTRACT FROM AUTHOR]

We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (Rq), average collagen content (A1) and collagen orientation (A12) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (Rc) had a significant coefficient of determination with Rq and A12 (RLMMm2=0.79); however, Rc did not correlate with A1. Concerning the collagen characteristic in the superficial zone, Rc was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. [ABSTRACT FROM AUTHOR]