Abstract #4292 The opposite sides of the same coin: Norepinephrine aggravates cartilage degeneration but attenuates subchondral bone changes

2019 ◽  
Vol 81 ◽  
pp. 23
Author(s):  
K. El Bagdadi ◽  
D. Muschter ◽  
S. Taheri ◽  
A. Meurer ◽  
F. Zaucke ◽  
...  
2003 ◽  
Vol 93 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Doreen Raudenbush ◽  
Dale R. Sumner ◽  
Parimal M. Panchal ◽  
Carol Muehleman

Osteoarthritis is a disease of synovial joints that involves articular cartilage breakdown with accompanying bone changes, including subchondral sclerosis and osteophytosis. However, conflicting data have been reported concerning the cause-and-effect relationship, if any, between these changes. The authors studied the subchondral plate (subchondral bone plus calcified cartilage) in relation to the degree of articular cartilage degeneration on the distal articular surface of the first metatarsal, a region prone to osteoarthritis. No correlation was found between subchondral plate thickness or porosity and the degree of cartilage degeneration in the study sample of 96 metatarsals. Owing to the suggestion that initiation of cartilage fibrillation may be a result of steep stiffness gradients in the subchondral bone, the ratios of subchondral plate thickness in adjacent regions of the metatarsal head were examined in detail, but no correlation was found with subchondral degeneration. Thus increases in subchondral bone thickness are not associated with increases in cartilage degeneration on the first metatarsal, which may imply that subchondral bone changes do not cause osteoarthritis in this joint. (J Am Podiatr Med Assoc 93(2): 104-110, 2003)


Author(s):  
L. G. E. Cox ◽  
C. C. van Donkelaar ◽  
B. van Rietbergen ◽  
K. Ito

Osteoarthritis (OA) affects both the articular cartilage and the subchondral bone. It is a complicated disease, associated with conditions varying from obesity and strenuous exercise to joint malalignment, anterior cruciate ligament (ACL) injury, and even metabolic bone diseases. Patients suffer from chronic joint pain and limitation of motion, and no cure is yet available. For many years, medical therapies have been focused on cartilage, because bone changes were thought not to play a major role in the OA disease process. However, it has been shown that bone changes occur in an early stage of OA, and that alterations to subchondral bone can lead to cartilage degeneration [1]. Therefore, currently the bone is considered as a therapeutic target as well.


2013 ◽  
Vol 65 (6) ◽  
pp. 1569-1578 ◽  
Author(s):  
Frank C. Ko ◽  
Cecilia Dragomir ◽  
Darren A. Plumb ◽  
Steven R. Goldring ◽  
Timothy M. Wright ◽  
...  

2021 ◽  
Author(s):  
◽  
Karima El Bagdadi

The pathogenesis of osteoarthritis (OA) involves articular cartilage, synovial tissue and subchondral bone and is therefore a disease of the whole joint. OA is characterized by progressive degradation of cartilage, synovial inflammation, osteophyte formation and subchondral bone sclerosis. Cartilage-surrounding tissues are innervated by tyrosine hydroxylase (TH)-positive sympathetic nerve fibers with the most important sympathetic neurotransmitter norepinephrine (NE) detected in the synovial fluid of OA patients. Furthermore, adrenergic receptors are expressed in different knee joint tissues. Most in vitro studies indicate a potential role of the β2-adrenergic receptor, which has been not investigated during OA pathogenesis in vivo. The role of the sympathetic nervous system (SNS) in OA progression has not yet been studied. Therefore, the objective of this study was to analyze how the SNS and NE influence the MSC dependent cartilage regeneration in vitro and the OA pathogenesis and manifestation in vivo. In the first part of this study, the effect of NE on the chondrogenesis of sASC, which are known to play an important role in cartilage regeneration was analyzed in vitro. In the second part of this study, the role of the SNS was studied in vivo in mice that were sympathectomized chemically followed by surgically induced OA. The specific focus was on the β2-adrenergic receptor effects on OA pathogenesis, which were analyzed in β2-adrenergic receptor-deficient mice. The in vitro experiments have shown that NE reduced the chondrogenic potential of sASCs by decreasing the expression of type II collagen and sGAG. NE mediated these effects mainly by the α2-AR signalling. Furthermore, NE treatment led to activation of the ERK1/2 signal pathway. These findings suggested that the sympathetic neurotransmitter NE might suppress the chondrogenic capacity of MSC and their dependent cartilage regeneration and may also play a role in OA progression and manifestation. The in vivo study has shown that sympathectomy reduced synovial TH-positive nerve fibers in the synovium and the NE concentration in the spleen significantly. In WT mice, DMM leads to increased NE concentrations in the spleen compared to sham mice indicating an increased SNS activity after mechanical stress or inflammation due to DMM. Sympathectomy leads to less pronounced cartilage degeneration (OARSI score) after DMM compared to DMM in WT mice. Furthermore, the release of the type II collagen degradation fragment CTX-II was abolished in Syx DMM mice compared to WT DMM mice, suggesting that less SNS activity due to sympathectomy reduced the cartilage degeneration during OA pathogenesis. Similarly, sympathectomy decreased the synovitis score significantly after DMM compared to DMM in WT mice. Synovitis in WT mice was accompanied by increased MMP-13 expression in the synovium after DMM, compared to Syx mice. Cartilage degeneration seemed to be driven mainly by the increased synovial inflammation accompanied by an increased MMP13 expression in synoviocytes and not in chondrocytes. The pathological changes in synovium and cartilage might also be linked to each other, as indicated by the moderate correlation between the synovial inflammation (synovitis score) and cartilage degeneration (OARSI score). Subchondral bone volume as well the thickness of the subchondral bone plate (SCBP) and calcified cartilage (CC) were increased in Syx mice compared to WT after DMM. The data on DMM induction in β2-AR deficient mice revealed that the β2-AR signaling is involved in cartilage degeneration and the aggravated subchondral bone changes as these mice had less pronounced cartilage degeneration compared to WT mice. While the cartilage degeneration was similar, the subchondral bone changes were more pronounced in β2-AR deficient mice compared to the Syx mice. Overall, the SNS had differential effects in cartilage, synovium and subchondral bone. A reduced SNS activity by sympathectomy attenuated cartilage degeneration and synovitis but aggravated the OA specific subchondral bone changes. These findings provide new insights into the development of novel therapeutic strategies for OA by targeting the SNS in a tissue- specific manner.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 825.2-826
Author(s):  
M. Jansen ◽  
A. Ooms ◽  
T. D. Turmezei ◽  
J. W. Mackay ◽  
S. Mastbergen ◽  
...  

Background:In addition to cartilage degeneration, knee osteoarthritis (OA) causes bone changes, including cortical bone thickening, subchondral bone density decrease, and bone shape changes as a result of widening and flattening condyles and osteophyte formation. Knee joint distraction (KJD) is a joint-preserving treatment for younger (<65 years) knee OA patients that has been shown to reverse OA cartilage degradation. On radiographs, KJD showed a decrease in subchondral bone density and an increase in osteophyte formation. However, these bone changes have never been evaluated with a 3D imaging technique.Objectives:To evaluate cortical bone thickness, subchondral trabecular bone density, and bone shape on CT scans before and one year after KJD treatment.Methods:19 KJD patients were included in an extended imaging protocol, undergoing a CT scan before and one year after treatment. Stradview v6.0 was used for semi-automatic tibia and femur segmentation from axial thin-slice (0.45mm) CT scans. Cortical bone thickness (mm) and trabecular bone density (Hounsfield units, HU) were measured with an automated algorithm. Osteophytes were excluded. Afterwards, wxRegSurf v18 was used for surface registration. Registration data was used for bone shape measurements. MATLAB R2020a and the SurfStat MATLAB package were used for data analysis and visualization. Two-tailed F-tests were used to calculate changes over time. Two separate linear regression models were used to show the influence of baseline Kellgren-Lawrence grade and sex on the changes over time. Statistical significance was calculated with statistical parametric mapping; a p-value <0.05 was considered statistically significant. Bone shape changes were explored visually using vertex by vertex displacements between baseline and follow-up. Patients were separated into two groups based on whether their most affected compartment (MAC) was medial or lateral. Only patients with axial CT scans at both time points available for analysis were included for evaluation.Results:3 Patients did not have complete CTs and in 1 patient the imaged femur was too short, leaving 16 patients for tibial analyses and 15 patients for femoral analyses. The MAC was predominantly the medial side (medial MAC n=14; lateral n=2). Before treatment, the MAC cortical bone was compared to the rest of the joint (Figure 1). One year after treatment, MAC cortical thickness decreased, although this decrease of up to approximately 0.25 mm was not statistically significant. The trabecular bone density was also higher before treatment in the MAC, and a decrease was seen throughout the entire joint, although statistically significant only for small areas on mostly the MAC where this decrease was up to approximately 80 HU (Figure 1). Female patients and patients with a higher Kellgren-Lawrence grade showed a somewhat larger decrease in cortical bone thickness. Trabecular density decreased less for patients with a higher Kellgren-Lawrence grade, and female patients showed a higher density decrease interiorly while male patients showed a higher decrease exteriorly. None of this was statistically significant. The central areas of both compartments showed an outward shape change, while the outer ring showed inward changes.Conclusion:MAC cortical bone thickness shows a partial decrease after KJD. Trabecular bone density decreased on both sides of the joint, likely as a direct result of the bicompartmental unloading. For both subchondral bone parameters, MAC values became more similar to the LAC, indicating (partial) subchondral bone normalization in the most affected parts of the joint. The bone shape changes may indicate a reversal of typical OA changes, although the inward difference that was seen on the outer edges may be a result of osteophyte-related changes that might have affected the bone segmentation. In conclusion, KJD treatment shows subchondral bone normalization in the first year after treatment, and longer follow-up might show whether these changes are a temporary result of joint unloading or indicate more prolonged bone changes.Disclosure of Interests:None declared.


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