Changes In Cartilage Metabolism Research Articles

Serum chemerin in a cohort of Colombian patients with primary osteoarthritis

Background and purposeOsteoarthritis (OA) is considered the most common degenerative joint pathology in the adult population, being an important cause of disability worldwide, and its prevalence is increasingly associated with different factors, including obesity. Obesity together with metabolic syndrome have been associated with a pro-inflammatory state due to the release of cytokines that induce changes in cartilage metabolism. Chemerin is an adipokine secreted mainly by adipocytes and its final action is to increase the production of IL-6, IL-8, IL-1b, TNF-a and metalloproteinases by macrophages, dendritic cells and chondrocytes, which are responsible for damage to the articular cartilage. This is one of the reasons that obesity and inflammation have been linked to OA. The main objective of this study is to determine whether the serum chemerin concentrations of a group of patients with primary OA are higher when compared with control individuals. A further purpose of the study is to determine the relationship between the presence of obesity/overweight with the severity of the disease measured by a radiological scale. Patients and methodsAn analytical cross-sectional study was carried out where serum chemerin levels were quantified by enzyme-linked immunoadsorption assay (ELISA), in patients with primary OA of the hip, knee and hand with criteria from the ACR (American College Of Rheumatology) and controls. Radiological studies of patients and controls were analysed to determine the severity of joint involvement using the Kellgren and Lawrence (KL) classification system. The statistical significance of the difference in serum chemerin values between the two groups was verified and the correlation between the variables of body mass index (BMI) with radiological severity, number of joint regions and serum chemerin levels was analysed. ResultsDuring the period from July 2015 to July 2016, serum samples and radiographs of compromised joints were collected from 40 patients with primary OA who met the inclusion criteria, as well as serum samples from 20 controls. The average concentration of chemerin was higher in the group of patients with OA compared to that of the control group, being 373ng / ml and 175.55ng / ml respectively (p<2.2×10–16). No significant associations were found between the different degrees of disease severity measured by the KL radiological scale, such as the number of involved joint regions and BMI. ConclusionsIn a group of patients with primary OA of the hand, knee or hip, the values of chemerin were higher than those found in controls, without significant association with the severity of the disease established radiologically by K/L scale, the number of involved joint regions, and the BMI.

Serum chemerin in a cohort of Colombian patients with primary osteoarthritis.

Osteoarthritis (OA) is considered the most common degenerative joint pathology in the adult population, being an important cause of disability worldwide, and its prevalence is increasingly associated with different factors, including obesity. Obesity together with metabolic syndrome have been associated with a pro-inflammatory state due to the release of cytokines that induce changes in cartilage metabolism. Chemerin is an adipokine secreted mainly by adipocytes and its final action is to increase the production of IL-6, IL-8, IL-1b, TNF-α and metalloproteinases by macrophages, dendritic cells and chondrocytes, which are responsible for damage to the articular cartilage. This is one of the reasons that obesity and inflammation have been linked to OA. The main objective of this study is to determine whether the serum chemerin concentrations of a group of patients with primary OA are higher when compared with control individuals. A further purpose of the study is to determine the relationship between the presence of obesity/overweight with the severity of the disease measured by a radiological scale. An analytical cross-sectional study was carried out where serum chemerin levels were quantified by enzyme-linked immunoadsorption assay (ELISA), in patients with primary OA of the hip, knee and hand with criteria from the American College Of Rheumatology (ACR) and controls. Radiological studies of patients and controls were analysed to determine the severity of joint involvement using the Kellgren and Lawrence (KL) classification system. The statistical significance of the difference in serum chemerin values between the two groups was verified and the correlation between the variables of body mass index (BMI) with radiological severity, number of joint regions and serum chemerin levels was analysed. During the period from July 2015 to July 2016, serum samples and radiographs of compromised joints were collected from 40 patients with primary OA who met the inclusion criteria, as well as serum samples from 20 controls. The average concentration of chemerin was higher in the group of patients with OA compared to that of the control group, being 373 ng / ml and 175.55 ng / ml respectively (p<2.2×10-16). No significant associations were found between the different degrees of disease severity measured by the KL radiological scale, such as the number of involved joint regions and BMI. In a group of patients with primary OA of the hand, knee or hip, the values of chemerin were higher than those found in controls, without significant association with the severity of the disease established radiologically by K/L scale, the number of involved joint regions, and the BMI.

The Effect of Vigorous Running and Cycling on Novel Markers of Knee Joint Function

To date, no study has been undertaken to compare the effects of running (weight-bearing) and cycling (non-weight bearing) exercise on biomarkers of knee joint loading. PURPOSE: To investigate knee articular cartilage deformation and changes in serum oligomteric matrix protein (COMP) and lubricin in response to vigorous recreational exercise. We tested the hypothesis that the mode of biomechanical loading of the knee joint (weight-bearing versus non-weight bearing) would influence the nature of the responses. METHODS: 11 male runners (age: 40±6 years; weight: 76±8 kg; VO2max: 4.3±0.3 L/min mean±SD) and 11 male cyclists (35±12 years; 75±5 kg; 4.4±0.6 L/min) were investigated. Venous blood samples and supra-patellar ultrasound imaging scans were obtained at baseline rest, immediately after, and 30 minutes after, vigorous exercise (time trial: either 10 km run or 25 km cycle). Knee cartilage thicknesses and serum COMP and lubricin (ELISA) were determined for each time point. Statistical analyses were performed using two-factor repeated measures (group x time) ANOVA. RESULTS: At baseline rest, there were no significant differences between groups for cartilage thicknesses measured at the intercondyle notch, medial condyle and lateral condyle. Vigorous exercise did not result in significant change in any of the cartilage thicknesses for either group. There were no significant differences between runners and cyclists for COMP (runners: 804.1±87.5 ng/ml; cyclists: 693.0±84.7 ng/ml) and lubricin (runners: 104.0±19.8 ng/ml; cyclists: 119.1±23.9 ng/ml) at baseline. For both groups, vigorous exercise was generally accompanied by an increase in both serum COMP (cyclists: 32.1%; p < 0.05; runners: 14.2%; p = 0.14) and lubricin (cyclists: 39.4%; p < 0.05; runners 56.9%; p < 0.05). Following 30 minutes of rest, serum COMP and lubricin decreased towards baseline values in both groups (p < 0.05). CONCLUSIONS: In the absence of ultrasonographic evidence of knee cartilage deformation, responses of lubricin following an acute bout of vigorous exercise is not influenced by the modality of knee joint loading, and may reflect a temporary increase in joint lubrication. However, changes in cartilage metabolism following exercise, as measured by serum COMP, may be dependent on the exercise modality.

Serum biochemical markers of joint metabolism and inflammation in relation to clinical symptoms and physical function in adults with symptomatic knee osteoarthritis

Purpose: To date, the majority of osteoarthritis (OA) biomarker research has examined associations between biomarker levels and radiographic parameters. While radiography provides information on the structural burden of disease, it is insensitive to small changes in cartilage metabolism and does not always correlate with the most significant clinical expression in OA, pain. The purpose of this study was to investigate the associations between joint metabolism and inflammation with pain and physical function in adults with painful knee OA. This is in support of qualifying burden of disease biomarkers with clinical variables to support the study, management, and understanding of disease pathology in OA. Methods: The study used baseline data from 54 adults with knee OA participating in a nutrition intervention study. The 100 mm visual analogue scale version of theWestern Ontario andMcMaster University Osteoarthritis Index (WOMAC) was used to assess pain, stiffness, and physical disability. A minimumWOMAC pain score of 125 was used as a cutoff for participant inclusion. Physical functionwas assessed with a 6minute walk test (:6MWT) and stair climb task (SCT). Serum concentrations of biomarkers included measures of cartilage degradation (cartilage oligomeric matrix protein [COMP]), cartilage synthesis (typeIIA collagen N-propeptide [PIIANP]), synovial metabolism (hyaluronic acid [HA]), cartilage degrading enzyme levels (matrix metalloproteinase 3 [MMP-3]), and inflammation (C-reactive protein [CRP]). COMP, PIIANP, HA, and MMP-3 were measured by enzyme-linked immunosorbent assay and CRP was measured by an immunoturbidimetric assay. Correlations between biomarkers and clinical variables were assessed using Spearman correlation coefficients. Results: Participants (38 females and 16 males) had a mean age of 60 11.9 years, BMI of 32.6 7.5 kg/m2, disease duration of 86.6 112.2 months, and WOMAC pain score of 193.4 94.04 mm. Higher serum MMP-3 levels were significantly associated with higher WOMAC pain scores (R 1⁄4 0.27, p 1⁄4 0.05), controlling for age and body mass index (BMI). Higher levels of serum HA were significantly associated with decreased walking distance in the :6MWT (R 1⁄4 -0.35, p 1⁄4 0.01) and longer time taken in the SCT (R 1⁄4 0.31, p 1⁄4 0.02), when controlling for age and BMI. Higher CRP levels were significantly associated with higher WOMAC physical disability score (R 1⁄4 0.34, p 1⁄4 0.01) and worse performance in the :6MWT (R1⁄4 -0.38, p1⁄4 0.005) and SCT (R1⁄4 0.44, p1⁄4 0.001) when age was controlled for, but these associations were not significant when BMI was controlled for. COMP and PIIANP were not significantly associated with any clinical variables analyzed. Conclusion: SerumMMP-3 levels were associated with pain and serum HA levels were associated with physical functioning in adults who suffer from mild to moderate pain and impaired physical functioning from knee OA. Previous studies have shown that HA and MMP-3 are related to structural knee parameters in OA. Therefore, results from this study demonstrate that serum HA and MMP-3 also have potential as qualified burden of disease biomarkers that are clinically meaningful. (Research supported by the Ontario Ministry of Agriculture, Food and Rural Affairs, project #200121).

The effect of environmental pH change on bovine articular cartilage metabolism: implications for the use of buffered solution during arthroscopy?

The purpose of this study is to determine the immediate effects of pH change on the metabolism of bovine chondrocytes. Bovine osteochondral explants were pre-cultured and placed in Ringer's lactate solution. Thirty explants were randomly divided into 3 groups. Buffered Ringer's lactate, pH 7.2, was used in Group I; buffered Ringer's lactate, pH 7.4 (normal bovine knee joint pH), was used in Group II; and this group was also set as the control group. Buffered Ringer's lactate, pH 7.6, was used in Group III. All specimens were soaked for 2 h. RNA yield analyses were performed to evaluate the changes in cartilage metabolism at different pH levels. Mean RNA yields of (hypoxia-induced factor) 1α that were immersed at pH 7.2 and 7.6 were 10.5- and 9.9-fold from base, respectively, which were lower compared to explants at pH 7.4 which was found as 15.2-fold. Mean RNA yields of aggrecan that were immersed at pH 7.2 and 7.6 were 12.2- and 13.6-fold from base, respectively, which were lower compared to explants at pH 7.4 which was found as 20-fold. RNA yields of collagen type II at pH 7.2 and 7.6 were 16.1- and 16.6-fold from base, respectively, which were lower compared to explants immersed at pH 7.4 which was found as 22.1-fold. The findings of the presented study suggest that short-term exposures to both acidic and basic pH may have effects on chondrocyte function. Our findings also indicate that exposures to solutions with a pH different from normal by only 0.2 unit could suppress chondrocyte metabolism and RNA synthesis. Using buffered irrigation solutions with a pH closer to the normal joint pH could be more physiologic and causes less ultra-structural damage than regular irrigation solutions. II.

The Effect of Irrigation Solution at Different Temperatures on Articular Cartilage Metabolism

The purpose of this study was to determine the effects of saline solution at different temperatures on the metabolism of chondrocytes. Porcine osteochondral explants were precultured under laboratory conditions. The cartilage explants were placed in saline solution. Twenty-four explants were randomly divided into 4 groups. Explants were immersed at 4°C group I, at room temperature (24°C) in group II, at normal knee temperature (32°C) in group III, and at near-core body temperature (37°C) in group IV. All specimens were immersed for 2 hours. Lactate and proteoglycan production and RNA yield analysis were performed to evaluate the changes in cartilage metabolism at different temperatures. Explants immersed in cold (4°C) saline solution showed the significantly lowest RNA yields, lactate production, and proteoglycan content. Explants immersed in cold solutions (4°C and 24°C) showed significantly lower RNA yields, lower lactate production, and lower proteoglycan content than explants in warmer solution groups (32°C and 37°C). The findings of this study suggest that short-term exposures to cold including room temperature may have markedly detrimental effects on chondrocyte function. Our findings also indicate that exposures to cold saline solution suppress chondrocyte metabolism and RNA synthesis. Using warmer irrigation solution that is closer to body temperature is more physiologic and causes less ultrastructural damage than colder solution.

SKI306X Suppresses Cartilage Destruction and Inhibits the Production of Matrix Metalloproteinase in Rabbit Joint Cartilage Explant Culture

SKI306X was previously found to have cartilage protective effects in the experimental osteoarthritis (OA) model. To investigate the chondro-protective benefits of SKI306X for its capacity in altering changes in cartilage metabolism and molecular mechanisms of cartilage protective action, SKI306X is studied in rabbit cartilage explants culture. To investigate the protective effect of SKI306X on cartilage catabolism, we assessed collagen degradation in rabbit cartilage explants treated with interleukin-1α up to 3 weeks. To examine the reaction mechanism, matrix metalloproteinase (MMPs) were investigated by fluorimetric and Western blotting analysis. In addition, its effects on the activation process of proenzyme MMP-3 were determined by gelatin zymography. SKI306X significantly inhibited collagen degradation and inhibited the activities of several MMPs. Total MMPs activities in cultured medium were substantially increased in the third week at the time of collagen degradation with the absence of SKI306. However, the introduction of SKI306X decreased MMPs activities in cultured medium. Furthermore, Western blotting analysis proved that these inhibitory effects of this drug were the result of inhibiting MMPs expression. SKI306X also inhibited the activation of proenzyme MMP-3 to the active form of MMP-3. These results indicate that SKI306X inhibits matrix degradation by down regulating MMPs expression and secretion, inhibition of MMPs activity, and inhibiting activation of MMP-3 during the collagen breakdown process.

Joint distraction in treatment of osteoarthritis (II): effects on cartilage in a canine model

Objective From a clinical point of view, joint distraction as a treatment for osteoarthritis (OA) of hip and ankle has been demonstrated to be very promising. Pain, joint mobility and functional ability, the most important factors for a patient with severe OA, all improved. Although radiographic joint space enlargement in a significant number of patients suggested cartilage repair, actual cartilage repair remains difficult to evaluate. Therefore the present study was initiated to evaluate the actual effects of joint distraction on cartilage.Methods For this purpose a canine model for OA, anterior cruciate ligament transection (ACLT) was used. Sixteen weeks after ACLT articulating Ilizarov joint distraction of the knee was carried out. Absence of mechanical contact between articular surfaces and presence of intra-articular intermittent fluid pressure, characteristics of Ilizarov joint distraction, were confirmed. Twenty-five weeks after ACLT joint tissue of the dogs was analyzed.Results Biochemical analysis showed that after joint distraction the abnormal cartilage proteoglycan (PG) metabolism, characteristic for OA, had changed to a level found in control joints. Moreover, a mild degree of inflammation, present after ACLT, was reduced upon joint distraction. PG-content and histological cartilage degeneration had not (yet) improved within the time of treatment.Discussion Results suggest that the promising clinical results of Ilizarov joint distraction in patients with OA are accompanied by changes in cartilage metabolism. A change in proteoglycan turnover, indicating normalization of overall chondrocyte function, might in the long term, with normal joint use, lead to actual repair of cartilage.{copy}

Proteoglycans in the synovial fluid of the temporomandibular joint as an indicator of changes in cartilage metabolism during primary and secondary osteoarthritis.

The specific aim of this investigation was to assess differences between primary and secondary osteoarthritis (OA) of the temporomandibular joint (TMJ) using clinical evaluation and synovial fluid analysis for proteoglycans. Arthroscopic surgery was performed on 101 TMJs from patients with significant pain or dysfunction and who had failed to respond to treatment. Joints were assessed for primary and secondary osteoarthritis. Synovial fluid aspirates were obtained and analyzed to determine the levels of keratan sulfate (KS) epitope and a novel 3B3(-) epitope by enzyme-linked immunosorbent assay (ELISA). Fifty-four patients and 67 joints had OA diagnosed by both clinical examination and arthroscopy. Primary OA was diagnosed in 14 joints (20%), and the remaining 53 joints were regarded as having secondary OA. No differences were detected in the levels of KS in the synovial fluid from the primary and secondary OA joints. Furthermore, the 3B3(-) epitope was not detectable in the synovial fluid aspirates of any TMJ. Secondary OA is a common disorder of the TMJ. However, there is no apparent difference in the metabolism of the joints with primary and secondary OA as assessed by proteoglycans in the synovial fluid. The apparent absence of the 3b3(-) epitope, in contrast to its presence in OA of other major synovial joints, suggests that there are some differences between the cartilage metabolism of the TMJ and these other joints during OA.

Changes in cartilage proteoglycan aggrecan after intra-articular injection of interleukin-1 in rabbits: studies of synovial fluid and articular cartilage.

To determine how acute but transient inflammation affects the cartilage proteoglycan aggrecan and the value of analyses of synovial fluid to study this. For 96 hours after a single intra-articular injection of rabbit knees with human interleukin-1 alpha (IL-1 alpha) or vehicle, articular cartilage and synovial fluid were examined using a putative indicator of aggrecan synthesis (aggrecan chondroitin sulphate epitope 846), immunoreactive keratan sulphate, and total glycosaminoglycan (GAG) content. Aggrecan extractability (with 0.5 M NaCl) followed by 4 M guanidine hydrochloride extraction permitted analyses of cartilage damage, total content and aggrecan heterogeneity. Aggrecan epitopes as well as GAG were assayed in synovial fluid. Changes were related to total joint leucocyte content in synovial fluid. At 10 ng, IL-1 alpha produced a transient increase in synovial fluid leucocytes at six hours and 24 hours. This accompanied a reduction in content and increased extractability of GAG, which was greatest in the tibial medial compartment of the knee. Further studies of this compartment showed no change in keratan sulphate epitope content, but a transient increase in extractability in 0.5 M NaCl. Epitope 846 content and extractability were unchanged. Total contents and extractability for GAG were inversely correlated in both controls and joints injected with IL-1 alpha. These changes were accompanied by transient increases in GAG, keratan sulphate epitope, and 846 content in synovial fluid. According to the aggrecan component measured, damage to the matrix of articular cartilage was sometimes reflected by a transient increased extractability and a net loss of aggrecan. There was always an increased release of GAG, and keratan sulphate, and 846 epitopes into synovial fluid. These studies show that changes in aggrecan epitopes and GAG in synovial fluid reflect changes in cartilage metabolism induced by acute transient inflammation.

Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases.

Effects of physicochemical factors on the growth of mandibular condyles in vitro.

Cartilage growth and remodeling are known to be influenced by the biochemical and mechanical environment of the tissue. Previous investigators have shown that chemical factors that are relevant to mechanical loading, such as osmotic pressure and pH, induce changes in cartilage metabolism in vitro. Using a neonatal rat mandibular condyle culture system, the objectives of the work reported here were to determine (1) how the growth is influenced by osmotically applied mechanical loads; and (2) whether changes in intratissue osmotic pressure or pH cause metabolic changes in the cartilage which are then reflected by altered growth behavior. High molecular weight (MW) uncharged macromolecules polyvinylpyrrolidone (PVP) and Ficoll (presumed unable to penetrate the tissue matrix) were used to examine the effect of osmotic loading on tissue growth; concentrations corresponding to osmotic pressures of up to 100 kPa resulted in a dose-dependent depression in growth and matrix accumulation. Raffinose (which can penetrate the matrix but not the cells) had no significant effect on growth for osmotic pressures of up to 87 kPa, suggesting that compression-induced changes in intratissue osmotic pressure are unlikely to provide a signal by which cells sense and respond to mechanical compression. By contrast, changes in medium pH resulted in dose-dependent changes in growth behavior. Specifically, slight alkalinity (acidity) greatly enhanced (diminished) growth and matrix accumulation; the sensitivity to pH suggests that intratissue pH could provide a mechanism for cells to sense local glycosaminoglycan concentration and mechanical compression.(ABSTRACT TRUNCATED AT 250 WORDS)

Markers of Articular Cartilage Injury and Healing

Molecules derived from cartilage are present in body fluids where they act as markers of the degradation or synthesis of specific components of the extracellular matrix of this shock-absorbing tissue. In joint fluid, the level of a marker molecule can be used to detect changes taking place in the cartilaginous tissues within that joint. In blood or urine, on the other hand, the level can be used to identify systemic changes or abnormalities affecting most or all the cartilages in the body. These specific markers of metabolic processes already have proved useful in identifying increased catabolic as well as anabolic activities in articular cartilage following traumatic knee joint injury. The markers are potentially useful for monitoring disease activity, identifying osteoarthritis in its preradiological stages, examining responses of the cartilaginous tissues to treatment and evaluating long-term prognosis. Markers should prove most useful in prospective studies aimed at identifying early changes in cartilage metabolism in humans who are at high risk of developing posttraumatic osteoarthritis.

BODY FLUID MARKERS OF CARTILAGE CHANGES IN OSTEOARTHRITIS

Various markers of the metabolism of articular cartilage have been identified in synovial fluid, blood, and urine of patients with osteoarthritis (OA). The joint fluid level of a cartilage-derived molecule, or its fragment, can be used as a marker of the synthesis or catabolism of that molecule in the articular surfaces within that joint. In blood and urine, on the other hand, the level of a marker is useful in assessing systemic changes affecting the metabolism of a molecule in all the cartilages in the body. Quantification of specific markers in body fluids already has proved useful in identifying increased catabolic as well as anabolic activities in articular cartilage during preradiologic as well as later stages of OA. The markers also can be sued for monitoring the effect of drugs on cartilage matrix molecules and in differentiating among different subtypes of osteoarthritis. Markers should prove most useful in prospective studies aimed at identifying early changes in cartilage metabolism in humans at high risk for developing OA.

Correlations between phases of deer antler regeneration and levels of serum keratan sulfate.

A sensitive and highly specific enzyme-linked immunosorbent assay with an inhibition step was used to monitor the concentration of keratan sulfate, a cartilage-related glycosaminoglycan, in the serum of three adult male deer. During the course of one complete annual antler regeneration cycle, keratan sulfate levels were found to fluctuate predictably in relation to the growth and maturation of the antlers: levels are substantially elevated during the growth phase and drop precipitously when growth ceases and the antlers become fully mineralized. In addition, an unanticipated elevation of serum keratan sulfate was observed in early spring prior to casting of the preceding year's antlers and the initiation of regrowth. This suggests that changes in cartilage metabolism occur concomitantly, with this phase of the antlerogenic cycle. These results show predictable and physiologically regulated variation in serum keratan sulfate levels which correlate directly with specific phases of the antler regeneration cycle. Furthermore, the findings provide additional support for the assertion that measurements of keratan sulfate levels in serum can provide useful information about changes in cartilage metabolism in normal as well as diseased states.

Decreases in ovine fetal cartilage sulfate uptake and serum sulfate during gestation.

In vitro assays for [35S]sulfate uptake by ovine fetal costal cartilage were used to assess gestational changes in cartilage metabolism. Addition of 20% normal human serum to the incubation medium increased fetal cartilage [35S]sulfate incorporation into glycosaminoglycans. Both basal and human serum-stimulated uptakes of [35S]sulfate by fetal sheep cartilage decreased from midgestation to full term. The incremental response in [35S]sulfate uptake that was stimulated by human serum decreased as gestation proceeded to full-term. Fetal serum sulfate concentration decreased logarithmically during gestation, raising the possibility that cartilage sulfate uptake might become substrate limited as full term is approached. Perfusion of seven late gestation sheep fetuses for 7 days with Na2SO4 to achieve serum sulfate concentrations similar to those observed earlier in gestation resulted in a 33% increase in mean cartilage [35S]sulfate uptake compared with that of control twin fetuses, but uptake was not increased to values that occurred spontaneously earlier in gestation. These results suggest that the decreasing rate of [35S]sulfate uptake by fetal cartilage during the last half of gestation is associated only minimally with decreasing serum sulfate levels and is most consistent with intrinsic change in resting chondrocyte metabolism during gestation.

A Reliable In Vivo Measurement of Bone-Mineral Content

The adverse effects of osteoarthritis on the quality of life for tens of millions of people and on the costs of health care and economic productivity make it a major health problem that will increase in incidence and impact with the aging of the population. Although in most patients the cause of osteoarthritis remains unknown and no cure has been identified, appropriate diagnosis and treatment, including education of the patients, can minimize symptoms and help patients maintain active and productive lives. Accomplishing this aim requires that physicians have an understanding of the pathophysiology of joint degeneration and the relationships between joint degeneration and the clinical syndrome of osteoarthritis. Although much remains to be learned about the development and progression of the joint degeneration responsible for osteoarthritis, it is clear that the loss of articular cartilage results from disruption of the structural integrity of the articular cartilage coupled with or caused by an imbalance in the anabolic and catabolic activity of the tissue. The progression of joint degeneration varies considerably among patients. In some individuals the joint degenerates rapidly; in others the degenerative changes progress slowly over decades and in others the disease may remain stable. In rare patients, the joint degenerative changes spontaneously improve. Although joint degeneration is the underlying cause of the symptoms of osteoarthritis, including joint pain and loss of joint function, not all patients with joint degeneration have symptoms of osteoarthritis. Future therapeutic approaches may include disease-modifying drugs and surgical procedures that correct mechanical abnormalities, debride joints, and replace degenerated articular cartilage with implants that stimulate restoration of a cartilaginous joint surface. Development of methods to detect and monitor subtle changes in cartilage metabolism and identify the joint changes that precede loss of articular cartilage may make it possible to detect the earliest signs of osteoarthritis, when therapeutic interventions have the greatest potential for preventing progression of the disease.