Early inhibition of subchondral bone remodeling slows load‐induced post‐traumatic osteoarthritis development in mice

2021 ◽  
Author(s):  
Sophia N. Ziemian ◽  
Ana Witkowski ◽  
Timothy M Wright ◽  
Miguel Otero ◽  
Marjolein C. H. Meulen
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone ◽  
Post Traumatic ◽  
Early Inhibition

scholarly journals Genetic Deletion of Interleukin-15 Is Not Associated with Major Structural Changes Following Experimental Post-Traumatic Knee Osteoarthritis in Rats

2021 ◽  
Vol 11 (15) ◽  
pp. 7118
Author(s):  
Ermina Hadzic ◽  
Garth Blackler ◽  
Holly Dupuis ◽  
Stephen James Renaud ◽  
Christopher Thomas Appleton ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Structural Changes ◽  
Cartilage Damage ◽  
Wild Type ◽  
Significant Difference ◽  
Post Traumatic ◽  
Interleukin 15 ◽  
Joint Trauma ◽  
Surgically Induced

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.

scholarly journals Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaobo Zhu ◽  
Yau Tsz Chan ◽  
Patrick S. H. Yung ◽  
Rocky S. Tuan ◽  
Yangzi Jiang
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Bone Remodeling ◽  
Molecular Mechanism ◽  
Subchondral Bone ◽  
Therapeutic Target ◽  
Therapeutic Targets ◽  
Regenerative Therapies

There is emerging awareness that subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). This review presents recent investigations on the cellular and molecular mechanism of subchondral bone remodeling, and summarizes the current interventions and potential therapeutic targets related to OA subchondral bone remodeling. The first part of this review covers key cells and molecular mediators involved in subchondral bone remodeling (osteoclasts, osteoblasts, osteocytes, bone extracellular matrix, vascularization, nerve innervation, and related signaling pathways). The second part of this review describes candidate treatments for OA subchondral bone remodeling, including the use of bone-acting reagents and the application of regenerative therapies. Currently available clinical OA therapies and known responses in subchondral bone remodeling are summarized as a basis for the investigation of potential therapeutic mediators.

scholarly journals Dihydroartemisinin attenuates osteoarthritis by inhibiting abnormal bone remodeling and angiogenesis in subchondral bone

2021 ◽  
Vol 47 (3) ◽  
Author(s):  
Long Ma ◽  
Xin Zhao ◽  
Yibin Liu ◽  
Jiang Wu ◽  
Xiaochun Yang ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone

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.

scholarly journals Noncoding RNAs in subchondral bone osteoclast function and their therapeutic potential for osteoarthritis

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Li Duan ◽  
Yujie Liang ◽  
Xiao Xu ◽  
Jifeng Wang ◽  
Xingfu Li ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Therapeutic Potential ◽  
Osteoclast Differentiation ◽  
Noncoding Rnas ◽  
Cartilage Degradation ◽  
Joint Disease ◽  
Molecular Signaling ◽  
Osteoclast Function

AbstractOsteoclasts are the only cells that perform bone resorption. Noncoding RNAs (ncRNAs) are crucial epigenetic regulators of osteoclast biological behaviors ranging from osteoclast differentiation to bone resorption. The main ncRNAs, including miRNAs, circRNAs, and lncRNAs, compose an intricate network that influences gene transcription processes related to osteoclast biological activity. Accumulating evidence suggests that abnormal osteoclast activity leads to the disturbance of subchondral bone remodeling, thus initiating osteoarthritis (OA), a prevalent joint disease characterized mainly by cartilage degradation and subchondral bone remodeling imbalance. In this review, we delineate three types of ncRNAs and discuss their related complex molecular signaling pathways associated with osteoclast function during bone resorption. We specifically focused on the involvement of noncoding RNAs in subchondral bone remodeling, which participate in the degradation of the osteochondral unit during OA progression. We also discussed exosomes as ncRNA carriers during the bone remodeling process. A better understanding of the roles of ncRNAs in osteoclast biological behaviors will contribute to the treatment of bone resorption-related skeletal diseases such as OA.

scholarly journals Age-Dependent Subchondral Bone Remodeling and Cartilage Repair in a Minipig Defect Model

2017 ◽  
Vol 23 (11) ◽  
pp. 745-753 ◽  
Author(s):  
Christian G. Pfeifer ◽  
Matthew B. Fisher ◽  
Vishal Saxena ◽  
Minwook Kim ◽  
Elizabeth A. Henning ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Cartilage Repair ◽  
Subchondral Bone ◽  
Defect Model ◽  
Age Dependent ◽  
And Cartilage

Subchondral bone remodeling increases in early experimental osteoarthrosis in young beagle dogs

1998 ◽  
Vol 69 (6) ◽  
pp. 627-632 ◽  
Author(s):  
Harri E Panula ◽  
Jyrki Nieminen ◽  
Jyrki J Parkkinen ◽  
Llkka Arnala ◽  
Heikki Kroger ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone ◽  
Beagle Dogs

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
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