Articular Calcified Cartilage Research Articles

CT imaging features of calcium pyrophosphate dihydrate crystal deposition involving spine

PurposeTo explore the computed tomography (CT) imaging features of the spine involved by calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) in order to improve the understanding of this disease. Materials and methodsAmong 79 patients diagnosed with CPPD-CDD in our hospital, 51 patients with spinal involvement were selected, 9 patients without CT examination were excluded, and 42 patients were finally included as research objects. The CT images of the 42 patients were retrospectively analyzed. The analysis contents mainly included the distribution of lesions and the characteristic imaging findings of intervertebral disc, posterior ligament complex, sacroiliac joint and atlantoaxial joint. ResultsIn this paper, 42 patients with 11 males and 31 females were studied. The onset age ranged from 62 to 95 years. There were 264 lesions in 42 patients with spinal involvement, including 177 lumbar vertebrae, 43 cervical vertebrae, 27 thoracic vertebrae and 17 sacroiliac joints (14 bilateral and 3 unilateral). Characteristic imaging findings include: disc calcification (129 cases), posterior ligament complex calcification (107 cases), sacroiliac articular cartilage calcification (17 cases), and ligaments around the odontoid process calcification (11 cases). ConclusionsThe characteristic images of CPPD-CDD involving the spine are calcification of intervertebral disc, posterior ligament complex, sacroiliac joint surface and ligaments around odontoid process, and the lesions are frequent and coexisting, so it should be differentiated from gout, rheumatoid arthritis, ankylosing spondylitis, ossification of ligamentum flavum, basic calcium phosphate and infectious spondylodiscitis.

Klf10 is involved in extracellular matrix calcification of chondrocytes alleviating chondrocyte senescence

Osteoarthritis (OA) is a chronic degenerative disease resulting joint disability and pain. Accumulating evidences suggest that chondrocyte extracellular matrix calcification plays an important role in the development of OA. Here, we showed that Krüppel-like factor 10 (Klf10) was involved in the regulation of chondrocyte extracellular matrix calcification by regulating the expression of Frizzled9. Knockdown of Klf10 attenuated TBHP induced calcification and reduced calcium content in chondrocytes. Restoring extracellular matrix calcification of chondrocytes could aggravate chondrocyte senescence. Destabilization of a medial meniscus (DMM) mouse model of OA, in vivo experiments revealed that knockdown Klf10 improved the calcification of articular cartilage and ameliorated articular cartilage degeneration. These findings suggested that knockdown Klf10 inhibited extracellular matrix calcification-related changes in chondrocytes and alleviated chondrocyte senescence.

Inhibiting Lysyl Oxidases prevents pathologic cartilage calcification

Lysyl oxidases (LOX(L)) are enzymes that catalyze the formation of cross-links in collagen and elastin fibers during physiologic calcification of bone. However, it remains unknown whether they may promote pathologic calcification of articular cartilage, an important hallmark of debilitating arthropathies. Here, we have studied the possible roles of LOX(L) in cartilage calcification, related and not related to their cross-linking activity. We first demonstrated that inhibition of LOX(L) by β-aminoproprionitrile (BAPN) significantly reduced calcification in murine and human chondrocytes, and in joint of meniscectomized mice. These BAPN’s effects on calcification were accounted for by different LOX(L) roles. Firstly, reduced LOX(L)-mediated extracellular matrix cross-links downregulated Anx5, Pit1 and Pit2 calcification genes. Secondly, BAPN reduced collagen fibrotic markers Col1 and Col3. Additionally, LOX(L) inhibition blocked chondrocytes hypertrophic differentiation (Runx2 and COL10), pro-inflammatory IL-6 release and reactive oxygen species (ROS) production, all triggers of chondrocyte calcification. Through unbiased transcriptomic analysis we confirmed a positive correlation between LOX(L) genes and genes for calcification, hypertrophy and extracellular matrix catabolism. This association was conserved throughout species (mouse, human) and tissues that can undergo pathologic calcification (kidney, arteries, skin). Overall, LOX(L) play a critical role in the process of chondrocyte calcification and may be therapeutic targets to treat cartilage calcification in arthropathies.

Adseverin, an actin-binding protein, modulates hypertrophic chondrocyte differentiation and osteoarthritis progression.

In osteoarthritis (OA), a disease characterized by progressive articular cartilage degradation and calcification, the articular chondrocyte phenotype changes and this correlates with actin cytoskeleton alterations suggesting that it regulates gene expression essential for proper phenotype. This study reports that OA is associated with the loss of adseverin, an actin capping and severing protein. Adseverin deletion (Adseverin-/-) in mice compromised articular chondrocyte function, by reducing F-actin and aggrecan expression and increasing apoptosis, Indian hedgehog, Runx2, MMP13, and collagen type X expression, and cell proliferation. This led to stiffer cartilage and decreased hyaline and increased calcified cartilage thickness. Together, these changes predisposed the articular cartilage to enhanced OA severity in Adseverin-/- mice who underwent surgical induction of OA. Adseverin-/- chondrocyte RNA sequencing and in vitro studies together suggests that adseverin modulates cell viability and prevents mineralization. Thus, adseverin maintains articular chondrocyte phenotype and cartilage tissue homeostasis by preventing progression to hypertrophic differentiation in vivo. Adseverin may be chondroprotective and a potential therapeutic target.

Sortilin Is Upregulated in Osteoarthritis-Dependent Cartilage Calcification and Associated with Cellular Senescence.

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage calcification, loss of articular cartilage, bone changes, pain, and disability. Cartilage calcification is one hallmark of OA and is predominantly caused by basic calcium crystals formed due to an imbalance of the pyrophosphate pathway. Sortilin is a transmembrane protein that contributes to vascular calcification in atherosclerosis by externalizing alkaline phosphatase (ALP)-containing vesicles. Calcification in atherosclerosis and osteoarthritis has been associated with cellular senescence. The aim of this study was to investigate the potential role of sortilin and senescence in osteoarthritis-dependent cartilage calcification. Osteoarthritic cartilage from human knee joints was collected after joint replacement, and samples were analyzed by immunohistochemistry and quantitative RT-PCR analysis. Human chondrocytes were treated with osteogenic medium for up to 21 days to induce calcification. Western blots for sortilin and ALP, as well as an ALP activity assay, were performed. Human chondrocytes were treated with mitomycin C to induce senescence, and sortilin expression was quantified at the protein and gene levels. Sections of knee joints from a murine model of osteoarthritis were stained for sortilin and p16 and analyzed by immunohistochemistry. Treatment of wild-type chondrocytes using an osteogenic medium similar to human chondrocytes was performed. Osteoarthritic cartilage from mouse and human knee joints showed an increased number of sortilin and p16-positive chondrocytes compared to healthy cartilage. This observation was corroborated by increased gene expression of sortilin and p16 in mild and moderate osteoarthritic cartilage samples. To investigate the mechanism of sortilin regulation, human chondrocytes were treated with osteogenic medium to induce calcification. Sortilin protein levels and expression were increased after 7 days of stimulation, whereas ALP levels and activity were upregulated after 21 days of stimulation. Similar observations were made in a murine osteoarthritis model. Mechanistically, senescent chondrocytes induced by mitomycin C showed an upregulation of sortilin and ALP gene expression compared to non-senescent chondrocytes. Our data indicate that sortilin and ALP are upregulated during cartilage calcification, which is associated with chondrocyte senescence and thus might contribute to the pathogenesis of osteoarthritis. Cellular senescence seems to induce sortilin expression.

Structural clues to articular calcified cartilage function: Adescriptive review of this crucial interface tissue.

Articular calcified cartilage (ACC) has been dismissed, by some, as a remnant of endochondral ossification without functional relevance to joint articulation or weight‐bearing. Recent research indicates that morphologic and metabolic ACC features may be important, reflecting knee joint osteoarthritis (OA) predisposition. ACC is less investigated than neighbouring joint tissues, with its component chondrocytes and mineralised matrix often being either ignored or integrated into analyses of hyaline articular cartilage and subchondral bone tissue respectively. Anatomical variation in ACC is recognised between species, individuals and age groups, but the selective pressures underlying this variation are unknown. Consequently, optimal ACC biomechanical features are also unknown as are any potential locomotory roles. This review collates descriptions of ACC anatomy and biology in health and disease, with a view to revealing its structure/function relationship and highlighting potential future research avenues. Mouse models of healthy and OA joint ageing have shown disparities in ACC load‐induced deformations at the knee joint. This raises the hypothesis that ACC response to locomotor forces over time may influence, or even underlie, the bony and hyaline cartilage symptoms characteristic of OA. To effectively investigate the ACC, greater resolution of joint imaging and merging of hierarchical scale data will be required. An appreciation of OA as a ‘whole joint disease’ is expanding, as is the possibility that the ACC may be a key player in healthy ageing and in the transition to OA joint pathology.

Acupotomy inhibits aberrant formation of subchondral bone through regulating osteoprotegerin/receptor activator of nuclear factor-κB ligand pathway in rabbits with knee osteoarthritis induced by modified Videman method.

To investigate the effects of acupotomy on inhibiting abnormal formation of subchondral bone in rabbits with knee osteoarthritis (KOA). A total of 24 New Zealand rabbits were randomly divided into four groups of 6 rabbits each [control, model, electroacupuncture (EA) and acupotomy]. Eighteen KOA model rabbits were established using a modified Videman method. Rabbits in EA and acupotomy groups received the intervention for 3 weeks. Then, the cartilage and subchondral bone unit were obtained and the histomorphological changes were recorded. Osteo-protegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in subchondral bone were evaluated by Western blotting, real-time polymerase chain reaction and immunohistochemistry. Compared with the model group, both the acupotomy and EA groups showed a significant decrease in the Lequesne index (both 0.01) and Mankin score ( 0.01, < 0.05). In addition, both EA and acupotomy groups had a higher expression of total articular cartilage (TAC) ( 0.05, < 0.01) and lower expression of articular calcified cartilage (ACC)/TAC ( 0.05, < 0.05) compared with the model group. The thickness of the subchondral bone plate in EA and acupotomy groups were decreased (both 0.01) compared to the model group. Moreover, trabecular bone volume (BV/TV), protein and relative expression of OPG and the ratio of OPG/RANKL in the subchondral bone of acupotomy group were decreased statistically significant, while these parameters were not significantly changed in the EA group compared with the model group. In the rabbit model of KOA, acupotomy inhibits aberrant formation of subchondral bone by suppressing OPG/RANKL ratio as a potential therapy for KOA.

Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization.

To study the mechanism by which the readthrough mutation in TNFRSF11B, encoding osteoprotegerin (OPG) with additional 19 amino acids at its C-terminus (OPG-XL), causes the characteristic bidirectional phenotype of subchondral bone turnover accompanied by cartilage mineralization in chondrocalcinosis patients. OPG-XL was studied by human induced pluripotent stem cells expressing OPG-XL and two isogenic CRISPR/Cas9-corrected controls in cartilage and bone organoids. Osteoclastogenesis was studied with monocytes from OPG-XL carriers and matched healthy controls followed by gene expression characterization. Dual energy X-ray absorptiometry scans and MRI analyses were used to characterize the phenotype of carriers and non-carriers of the mutation. Human OPG-XL carriers relative to sex- and age-matched controls showed, after an initial delay, large active osteoclasts with high number of nuclei. By employing hiPSCs expressing OPG-XL and isogenic CRISPR/Cas9-corrected controls to established cartilage and bone organoids, we demonstrated that expression of OPG-XL resulted in excessive fibrosis in cartilage and high mineralization in bone accompanied by marked downregulation of MGP, encoding matrix Gla protein, and upregulation of DIO2, encoding type 2 deiodinase, gene expression, respectively. The readthrough mutation at CCAL1 locus in TNFRSF11B identifies an unknown role for OPG-XL in subchondral bone turnover and cartilage mineralization in humansvia DIO2 and MGP functions. Previously, OPG-XL was shown to affect binding between RANKL and heparan sulphate (HS) resulting in loss of immobilized OPG-XL. Therefore, effects may be triggered by deficiency in the immobilization of OPG-XL Since the characteristic bidirectional pathophysiology of articular cartilage calcification accompanied by low subchondral bone mineralization is also a hallmark of OA pathophysiology, our results are likely extrapolated to common arthropathies.

CALCIFICATION AND PROTEOGLYCAN SULFATION IN OSTEOARTHRITIS AND CHONDROCALCINOSIS

Purpose: Osteoarthritis (OA) and chondrocalcinosis (CC) are common arthropathies associated with the accumulation of calcium-containing crystals in the cartilage and synovial membrane. Basic calcium phosphate (BCP) crystals are present in OA, whereas calcium phosphate dehydrate (CPPD) crystals are a characteristic of CC. Further, BCP crystals have been linked to Wnt signaling and hypertrophic differentiation of chondrocytes, whereas CPPD crystals may be responsible for chondrocyte senescence. Despite their association with different types of calcium crystals, OA and CC share similar phenotypes including a progressive degeneration and calcification of articular cartilage.

Thickness determination of the tidemark of human articular cartilage using high-resolution micro-XRF imaging of zinc and lead

ObjectiveThe objective of the study was to specify the thickness of Zn and Pb accumulation within the tidemark (TM), a narrow structure between the non-calcified and the calcified articular cartilage. It is considered an active or resting calcification front. This banded structure of the cartilage-bone interface is known to undergo changes in osteoarthritis. Therefore, gaining knowledge about this structure is of interest. MethodsFemoral head samples were collected from patients suffering from various bone diseases, 6 samples have been investigated. Thin bone slices (3 ​μm thick) were measured with high resolution synchrotron micro-X-ray fluorescence (SR micro-XRF) analysis using a beam with dimensions of 500 ​× ​800 ​nm2. The tidemark region was found in all analyzed samples. The Savitzky-Golay filter was used to smooth the measured imaging data and Kaplan-Meier estimation to gain reliable tidemarks medians for Pb and Zn. To our knowledge this was the first time that these methods have been applied to gain information on histological structures obtained by elemental imaging. ResultsThe thickness of the Zn and Pb layer ranged from about 3 to 11 ​μm for Zn and 4–14.5 ​μm for Pb. Our Zn ratios (TM/matrix) were found to be 1.5-3-fold ratio between Zn tidemark values and in mineralized matrix and are similar in all samples. ConclusionsThe determined thickness of the layer is much smaller than found in previous measurements with the beam having 20 ​× ​14 ​μm2 size. The Zn ratios agree with our previous findings.

A comparison between high density mineralised protrusions identified in the knees of cadavers and in patients of the osteoarthritis initiative

Purpose: Fatigue-induced microcracking is a common, naturally occurring phenomenon in articular calcified cartilage and subchondral bone (SCB). These microcracks are, in some cases, healed by infilling with and mineralisation of an aqueous matrix. High density mineralised protrusions (HDMP) of the same matrix from the tidemark mineralising front into hyaline articular cartilage (HAC) form as an aberrant by-product of this aresorptive repair mechanism. First discovered in equine joints, HDMPs have now been confirmed on the articular surfaces of femoral heads in humans with ochronotic and conventional osteoarthritis (OA).

Prematurely aging mitochondrial DNA mutator mice display subchondral osteopenia and chondrocyte hypertrophy without further osteoarthritis features

Mitochondrial mutations and dysfunction have been demonstrated in several age-related disorders including osteoarthritis, yet its relative contribution to pathogenesis remains unknown. Here we evaluated whether premature aging caused by accumulation of mitochondrial DNA mutations in PolgD275A mice predisposes to the development of knee osteoarthritis. Compared with wild type animals, homozygous PolgD275A mice displayed a specific bone phenotype characterized by osteopenia of epiphyseal trabecular bone and subchondral cortical plate. Trabecular thickness was significantly associated with osteocyte apoptosis rates and osteoclasts numbers were increased in subchondral bone tissues. While chondrocyte apoptosis rates in articular and growth plate cartilage were similar between groups, homozygous mitochondrial DNA mutator mice displayed elevated numbers of hypertrophic chondrocytes in articular calcified cartilage. Low grade cartilage degeneration, predominantly loss of proteoglycans, was present in all genotypes and the development of osteoarthritis features was not found accelerated in premature aging. Somatically acquired mitochondrial DNA mutations predispose to elevated subchondral bone turnover and hypertrophy in calcified cartilage, yet additional mechanical or metabolic stimuli would seem required for induction and accelerated progression of aging-associated osteoarthritis.

Concentric lamellae \u2013 novel microanatomical structures in the articular calcified cartilage of mice

The structure, ultrastructure and function of hyaline articular cartilage (HAC) and subchondral bone (SCB), and their involvement in the pathogenesis of osteoarthritis (OA) have been extensively researched. However, much less attention has been focused on the intervening tissue, articular calcified cartilage (ACC) and its role in the initiation and progression of OA. Using both light microscopy (LM) and transmission electron microscopy (TEM), a study of ACC in wild type (WT) mice, and mice with genetic osteoarthropathies (AKU) was undertaken to further understand the role played by ACC in the early stages of OA.Tibio-femoral joints were obtained from BALB/c WT and BALB/c AKU mice aged between 7 and 69 weeks. One joint was processed for routine histological analysis. The tip of the medial femoral condyle (MFC), which contained HAC, ACC, and SCB, was dissected from the contra-lateral joint and processed for TEM.In WT and AKU mice novel microanatomical structures, designated concentric lamellae, were identified surrounding chondrocytes in the ACC. The lamellae appeared to be laid down in association with advancement of the tidemark indicating they may be formed during calcification of cartilage matrix. The lamellae were associated with hypertrophic chondrocytes throughout the ACC.Novel microanatomical structures, termed concentric lamellae, which were present around hypertrophic chondrocytes in the ACC are described for the first time. Their apparent association with mineralisation, advancement of the tidemark, and greater abundance in a model of osteoarthropathy indicate their formation could be important in the pathogenesis of OA and AKU.

Longitudinal survey for high density mineralised protrusions identified by 3D dess MRI in patients of the osteoarthritis initiative

Purpose: The structural and physiological integrity of the bone-cartilage interface is essential to maintaining joint health. Phenomena that disrupt this boundary can compromise whole joint function and are a major factor in the development of osteoarthritis (OA), particularly in the knee. Early diagnosis of such maladies may offer a predictive biomarker of joint destruction. Microcracks in the subchondral bone plate including the articular calcified cartilage (ACC) are in some cases repaired with a high density mineralised infill material. This material may also extend from the mineralising front into hyaline articular cartilage (HAC) as a high density mineralised protrusion (HDMP). Such features are likely to impair biomechanical performance of surrounding tissues. Their formation can occur in the absence of symptomatic OA and they are potentially a primary cause of OA. Recent reports have confirmed the presence of HDMPs in human ex- and in-vivo knee joints and their detectability with clinical MRI. Here we present the first longitudinal MRI study prospecting for HDMPs in the human knee. Methods: Twenty-one patients were selected from the osteoarthritis initiative (OAI) progression cohort for whom bilateral knee MRI data were available at five consecutive annual visits. Sagitally-acquired dual echo steady state MRI images were assessed for the presence of HDMP-like features at baseline. Incidences were recorded and categorised to one of six regions according to bone and laterality: medial femoral condyle (MFC), lateral femoral condyle (LFC), intercondylar fossa of femur (ICF), medial tibial condyle (MTC), lateral tibial condyle (LTC) and intercondylar ridge of tibia (ICT). Imaging data from follow-up visits were used to monitor the development of features over time. Results: Seventeen patients were found to possess MRI features identified as HDMPs in at least one knee with incidence being unilateral in 5 and bilateral in 12 cases. A total of 58 features were found, ranging from 1 to 5 in a single joint. Features were found in all six regions of the knee joint but distribution between regions was inequitable with 73% being located somewhere on the femur (ICF = 36%; LFC = 25%; MFC = 12%) and only 27% on the tibia (LTC = 23%; MTC = 2%; ICT = 2%). Of those HDMPs identified at baseline, the percentage still present at each subsequent annual visit was 96, 90, 85 and 81, respectively. Morphology of those still visible varied greatly; some remained similar in appearance while others altered substantially, for example, changing in size and shape. Some appeared to have fragmented, forming clusters within HAC. Figure 1 shows an example of a HDMP located on the articular surface of the medial femoral condyle. The material extends from the subchondral bone surface initially. It can be seen breaking away and moving gradually through HAC over time. Conclusions: Observation of features in regions of high mechanical stress and noting their disappearance over time is suggestive of a role in arthropathy. Fine particles of fragmented HDMP may abrade HAC and damage surrounding tissue. The potential for mineral features to fragment may account for apparent clustering of features over time, or they may be discrete incidences. Longevity of features throughout the study duration suggests fragmentation is slow and not guaranteed. Disappearance may indicate destruction or may be caused by average effects. The lower proportion of HDMPs in tibiae may indicate the bone is less susceptible to HDMP formation, or they may be shorter lived. The appearances of HDMPs in clinical scans were consistent with reported ex-vivo studies. Clinical DESS yields high contrast between signal intensities of mineral (low yield) and HAC (high yield) and the features described should be considered a potential imaging biomarker for the prediction of joint destruction in some forms of OA.

The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs.

Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs. Subchondral bone advance was greater in the control Hartley guinea pigs compared with PC- or PC analogue-treated guinea pigs. Resorption of cartilage bars or islands and vascular invasion in the growth plate were also greater in the control guinea pigs compared with the PC- or PC analogue-treated guinea pigs. The levels of matrix metalloproteinase-13 and type X collagen within the articular cartilage and growth plate were significantly increased in the control guinea pigs compared with PC-treated guinea pigs (P<0.05). These results indicated that articular chondrocytes in Hartley guinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification. Activation of this molecular program resulted in resorption of calcified articular cartilage and subchondral bone advance. This suggests that PC and PC analogues exerted their OA disease-modifying activity, in part, by inhibiting this molecular program.

The effect of the sagittal ridge angle on cartilage stress in the equine metacarpo-phalangeal (fetlock) joint

Fatigue failure of bones of the metacarpo-phalangeal (fetlock, MCP) joint is common in thoroughbred racehorses. Stresses within the fetlock joint cartilages are affected by the morphology of the third metacarpal bone (MC3) and proximal phalangeal bone, and the steepness of the median sagittal ridge of MC3 is believed to be associated with fracture. This study investigated the influence of the steepness of the sagittal ridge on cartilage stress distribution using a finite element model of the joint. Changes to the steepness of the sagittal ridge were made by applying a parabolic function to the mesh, creating four different models with sagittal ridge angles ranging from 95° to 105°. In the fetlock joint of Thoroughbred racehorses, sagittal ridge angles of >100° were associated with higher Von Mises stresses in cartilage at the palmar aspect of the condylar groove than such stresses in joints with sagittal ridge angles of <100°. Stresses were high in the specific region where fractures are known to originate in MC3. This aspect of morphology of the fetlock joint thus appears to play an important role in the magnitude and distribution of cartilage stresses, which, when acting on the underlying hard tissues of the articular calcified cartilage and subchondral bone may play a role in the initiation of fatigue fracture in the third metacarpal bone.

RESEARCH PROGRESS OF PATHOLOGY OF ENDOCHONDRAL OSSIFICATION IN OSTEOARTHRITIS

To summarize the research progress of pathological manifestations and mechanism of endochondral ossification in osteoarthritis (OA). The literature about endochondral ossification, bone-cartilage remodeling in OA, and joints development was reviewed, analyzed, and summarized. Chondrocyte hypertrophy and apoptosis, vascular invasion, replication of the tidemark, thickening calcified cartilage, and thinning superficial cartilage are the characteristics of cartilage degeneration in OA. Articular cartilage and growth plate are similar in structure, and cartilage degeneration in OA is similar to a process of endochondral ossification of the growth plate. Loss of stability characterization from resting metabolic balance to a high conversion state of temporary cartilage in stimulation of abnormal mechanical stresses and cytokines would subsequently contributed to continual calcification and remodeling of articular cartilage, which may be the key link of the initiation and development of OA.

Articular cartilage calcification of the hip and knee is highly prevalent, independent of age but associated with histological osteoarthritis: evidence for a systemic disorder

Based on the concept of a systemic predisposition for articular cartilage calcification (CC), the aim of this study was to determine the prevalence and amount of bilateral CC of hip and knee joints in an unselected sample cohort by high-resolution digital contact radiography (DCR) and to analyze the association of CC with histological OA. Both hip and knee joints of 87 donors (48m and 39f; mean age 62) were analyzed by DCR in this post-mortem study of an unselected cohort of donors. Histological OA (OARSI) of the main load bearing area of femoral heads and medial femoral condyles was determined. The prevalence of CC of the femoral head was 96.6%, of the knee 94.3%. Bilateral calcification was detected in 79.3% of hips and 86.2% of knees. Concomitant CC of all four joints was detected in 69.0% of donors. There was no difference between the amount of CC of hips and knees (P=0.47). The amount of CC of any given hip or knee correlated with that of the contralateral hip (rs=0.54, P<0.001) or knee (rs=0.50, P<0.001). There was a correlation between the amount of CC and histological OA (hips rs=0.48, P<0.001, knees rs=0.30, P=0.004), but not between CC and age (hips rs=-0.09, P=0.42; knees rs=0.10, P=0.34). These data support the concept that articular CC occurs as the result of a systemic disorder. CC appears to be an early element of hip and knee OA pathogenesis independent of age.

Articular cartilage calcification of the humeral head is highly prevalent and associated with osteoarthritis in the general population.

Articular cartilage calcification is considered a pathological albeit incompletely understood process which is known to be associated with osteoarthritis of the knee and hip. The goal of this study was to determine the prevalence of articular cartilage calcification of the shoulder as a non-weight-bearing joint and to analyze the interrelationship of calcification with age and histological severity of shoulder osteoarthritis in the general population. In a cross-sectional study of 180 humeral heads from 90 donors (n = 49 male, n = 41 female; mean age 62.7 years [20-93]), cartilage calcification of the humeral head was quantified by digital contact radiography (DCR). Histological OA grade (OARSI) was determined and structural equation modeling (SEM) was used to analyze the interrelationship of cartilage calcification, OARSI and age. The prevalence of articular cartilage calcification was 98.9% (95%CI: [93.96%, 99.97%]) and was independent of gender (p = 0.55). Cartilage calcification of one shoulder correlated significantly with that of the contralateral side (r = 0.61, 95%CI: [0.46, 0.73], p < 0.001). SEM demonstrated significant associations between histological OA grade and cartilage calcification (r = 0.55, p = 0.039), between histological OA grade and age (β = 0.59, p < 0.001) but not between age and cartilage calcification (β = 0.24, p = 0.116). In conclusion, the prevalence of shoulder cartilage calcification in the general population is higher than anticipated. The high prevalence, its concomitant bilateral manifestation and the association between the amount of cartilage calcification and OA severity, but not age, suggest that cartilage calcification is a systemically driven process with early onset in life and may be a causative factor in the pathogenesis of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1984-1990, 2016.

Osteoclasts are recruited to the subchondral bone in naturally occurring post-traumatic equine carpal osteoarthritis and may contribute to cartilage degradation

The role of osteoclasts in osteochondral degeneration in osteoarthritis (OA) has rarely been investigated in spontaneous disease or animal models of OA. The objectives of the current study were to investigate osteoclast density and location in post-traumatic OA (PTOA) and control specimens from racehorses. Cores were harvested from a site in the equine third carpal bone, that undergoes repetitive, high intensity loading. Histological and immunohistochemical (Cathepsin K and Receptor-activator of Nuclear Factor kappa-β ligand (RANKL)) stained sections were scored (global and subregional) and the osteoclast density calculated. The cartilage histological scores were compared with osteoclast density and RANKL scores. There was a greater density of osteoclasts in PTOA samples and they were preferentially located in the subchondral bone plate. RANKL scores positively correlated to the scores of cartilage degeneration and the osteoclast density. The relationship between hyaline articular cartilage RANKL score and osteoclast density was stronger than that of the subchondral bone RANKL score suggesting that cartilage RANKL may have a role in recruiting osteoclasts. The RANKL score in the articular calcified cartilage correlated with the number of microcracks also suggesting that osteoclasts recruited by RANKL may contribute to calcified cartilage degeneration in PTOA. Our results support the hypothesis that osteoclasts are recruited during the progression of spontaneous equine carpal PTOA by cartilage RANKL, contributing to calcified cartilage microcracks and focal subchondral bone loss.