scholarly journals β2-Adrenoceptor Deficiency Results in Increased Calcified Cartilage Thickness and Subchondral Bone Remodeling in Murine Experimental Osteoarthritis

2022 ◽  
Vol 12 ◽  
Author(s):  
Gundula Rösch ◽  
Dominique Muschter ◽  
Shahed Taheri ◽  
Karima El Bagdadi ◽  
Christoph Dorn ◽  
...  
Keyword(s):  
Body Weight ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Plate Thickness ◽  
Cathepsin K ◽  
Cartilage Degeneration ◽  
Synovial Inflammation ◽  
Serum Leptin ◽  
Knee Oa ◽  
Calcified Cartilage

PurposeRecent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of knee OA in β2-AR-deficient (Adrb2-/-) mice after surgical OA induction.MethodsOA was induced by destabilization of the medial meniscus (DMM) in male wildtype (WT) and Adrb2-/- mice. Cartilage degeneration and synovial inflammation were evaluated by histological scoring. Subchondral bone remodeling was analyzed using micro-CT. Osteoblast (alkaline phosphatase - ALP) and osteoclast (cathepsin K - CatK) activity were analyzed by immunostainings. To evaluate β2-AR deficiency-associated effects, body weight, sympathetic tone (splenic norepinephrine (NE) via HPLC) and serum leptin levels (ELISA) were determined. Expression of the second major AR, the α2-AR, was analyzed in joint tissues by immunostaining.ResultsWT and Adrb2-/- DMM mice developed comparable changes in cartilage degeneration and synovial inflammation. Adrb2-/- DMM mice displayed elevated calcified cartilage and subchondral bone plate thickness as well as increased epiphyseal BV/TV compared to WTs, while there were no significant differences in Sham animals. In the subchondral bone of Adrb2-/- mice, osteoblasts activity increased and osteoclast activity deceased. Adrb2-/- mice had significantly higher body weight and fat mass compared to WT mice. Serum leptin levels increased in Adrb2-/- DMM compared to WT DMM without any difference between the respective Shams. There was no difference in the development of meniscal ossicles and osteophytes or in the subarticular trabecular microstructure between Adrb2-/- and WT DMM as well as Adrb2-/- and WT Sham mice. Number of α2-AR-positive cells was lower in Adrb2-/- than in WT mice in all analyzed tissues and decreased in both Adrb2-/- and WT over time.ConclusionWe propose that the increased bone mass in Adrb2-/- DMM mice was not only due to β2-AR deficiency but to a synergistic effect of OA and elevated leptin concentrations. Taken together, β2-AR plays a major role in OA-related subchondral bone remodeling and is thus an attractive target for the exploration of novel therapeutic avenues.

Subchondral Thickness Does Not Vary with Cartilage Degeneration on the Metatarsal

2003 ◽  
Vol 93 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Doreen Raudenbush ◽  
Dale R. Sumner ◽  
Parimal M. Panchal ◽  
Carol Muehleman
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Articular Surface ◽  
Plate Thickness ◽  
Cartilage Degeneration ◽  
Metatarsal Head ◽  
First Metatarsal ◽  
Calcified Cartilage ◽  
Bone Changes ◽  
Subchondral Plate

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)

scholarly journals Noggin Inhibits IL-1β and BMP-2 Expression, and Attenuates Cartilage Degeneration and Subchondral Bone Destruction in Experimental Osteoarthritis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 927 ◽  
Author(s):  
Szu-Yu Chien ◽  
Chun-Hao Tsai ◽  
Shan-Chi Liu ◽  
Chien-Chung Huang ◽  
Tzu-Hung Lin ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathways ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Bone Destruction ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Mitogen Activated Protein Kinase ◽  
Bone Morphogenetic Protein 2 ◽  
Joint Disease

Osteoarthritis (OA) is a chronic inflammatory and progressive joint disease that results in cartilage degradation and subchondral bone remodeling. The proinflammatory cytokine interleukin 1 beta (IL-1β) is abundantly expressed in OA and plays a crucial role in cartilage remodeling, although its role in the activity of chondrocytes in cartilage and subchondral remodeling remains unclear. In this study, stimulating chondrogenic ATDC5 cells with IL-1β increased the levels of bone morphogenetic protein 2 (BMP-2), promoted articular cartilage degradation, and enhanced structural remodeling. Immunohistochemistry staining and microcomputed tomography imaging of the subchondral trabecular bone region in the experimental OA rat model revealed that the OA disease promotes levels of IL-1β, BMP-2, and matrix metalloproteinase 13 (MMP-13) expression in the articular cartilage and enhances subchondral bone remodeling. The intra-articular injection of Noggin protein (a BMP-2 inhibitor) attenuated subchondral bone remodeling and disease progression in OA rats. We also found that IL-1β increased BMP-2 expression by activating the mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and specificity protein 1 (Sp1) signaling pathways. We conclude that IL-1β promotes BMP-2 expression in chondrocytes via the MEK/ERK/Sp1 signaling pathways. The administration of Noggin protein reduces the expression of IL-1β and BMP-2, which prevents cartilage degeneration and OA development.

Calcified cartilage morphometry and its relation to subchondral bone remodeling in equine arthrosis

Bone ◽  
1999 ◽  
Vol 24 (2) ◽  
pp. 109-114 ◽  
Author(s):  
R.W Norrdin ◽  
C.E Kawcak ◽  
B.A Capwell ◽  
C.W McIlwraith
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone ◽  
Calcified Cartilage

scholarly journals Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model

2013 ◽  
Vol 34 (3) ◽  
pp. 393-402 ◽  
Author(s):  
De-gang Yu ◽  
Hui-feng Ding ◽  
Yuan-qing Mao ◽  
Ming Liu ◽  
Bo Yu ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone ◽  
Strontium Ranelate ◽  
Cartilage Degeneration

scholarly journals Mineral crystal thickness in calcified cartilage and subchondral bone in healthy and osteoarthritic knees

2021 ◽  
Author(s):  
Mikko A.J. Finnilä ◽  
Shuvashis Das Gupta ◽  
Mikael J. Turunen ◽  
Iida Kestilä ◽  
Aleksandra Turkiewicz ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Wide Spectrum ◽  
Disease Process ◽  
Lateral Compartment ◽  
Medial Compartment ◽  
Joint Disease ◽  
Crystal Thickness ◽  
Knee Oa ◽  
Mineral Crystal ◽  
Calcified Cartilage

Osteoarthritis (OA) is the most common joint disease globally. In OA, articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. Especially, it is technically challenging to identify calcified cartilage, where relevant but poorly understood pathological processes like tidemark multiplication and advancement occur. Here, we used state-of-the art micro-focus small-angle X-ray scattering with high 5μm spatial resolution to determine mineral crystal thickness in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from the medial and lateral compartments of medial compartment knee OA patients (n=15) and cadaver knees (n=10). For the first time, we identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32nm thicker crystals compared to the rest of calcified cartilage. In addition, we found 0.2nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process since the lateral compartment is typically less loaded in medial compartment knee OA. Furthermore, the crystal thickness of the subchondral bone was lower with increasing histopathological OA severity. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee is associated with the growth of mineral crystals, which is especially evident in the calcified cartilage. In the subchondral bone, mineral crystals become thinner with increasing OA severity, which indicates new bone formation with sclerosis.

scholarly journals Serum Leptin Concentration Positively Correlates with Body Weight and Total Fat Mass in Postmenopausal Japanese Women with Osteoarthritis of the Knee

Arthritis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Jun Iwamoto ◽  
Tsuyoshi Takeda ◽  
Yoshihiro Sato ◽  
Hideo Matsumoto
Keyword(s):  
Body Weight ◽  
Regression Analysis ◽  
Lumbar Spine ◽  
Bone Turnover ◽  
Fat Mass ◽  
Whole Body ◽  
Serum Leptin ◽  
Knee Oa ◽  
Total Fat ◽  
Turnover Markers

The objective of the present study was to identify factors correlated with the serum leptin concentration in women with knee OA. Fifty postmenopausal Japanese women with knee OA (age: 50–88 years) were recruited in our outpatient clinic. Plain radiographs of the knee were taken, and urine and blood samples were collected. Dual-energy X-ray absorptiometry (DXA) scanning was performed for the whole body and lumbar spine, and factors correlated with the serum leptin concentration were identified. A simple linear regression analysis showed that body weight, body mass index, whole-body bone mineral density (BMD), total fat mass, and total fat percentage, but not age, height, lumbar spine BMD, lean body mass, serum and urinary bone turnover markers, or the radiographic grade of knee OA, were significantly correlated with the serum leptin concentration. A multiple regression analysis showed that among these factors, only body weight and total fat mass exhibited a significant positive correlation with the serum leptin concentration. These results suggest that the serum leptin concentration might be related to increases in body weight and total fat mass, but not to BMD or bone turnover markers, in postmenopausal women with OA.

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