Articular Cartilage Degradation and Aberrant Subchondral Bone Remodeling in Patients with Osteoarthritis and Osteoporosis

2019 ◽  
Vol 35 (3) ◽  
pp. 505-515 ◽  
Author(s):  
Linyang Chu ◽  
Xuqiang Liu ◽  
Zihao He ◽  
Xuequan Han ◽  
Mengning Yan ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Cartilage Degradation

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 Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Weiping Lin ◽  
Zhengmeng Yang ◽  
Liu Shi ◽  
Haixing Wang ◽  
Qi Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Subchondral Bone ◽  
Peripheral Blood ◽  
Cartilage Degradation ◽  
Cartilage Tissue ◽  
Synovial Joint ◽  
Post Surgery ◽  
Sham Surgery

Abstract Background: Osteoarthritis (OA) is a chronic joint disease, characterized by articular cartilage degradation, subchondral bone hardening, and inflammation of the whole synovial joint. There is no pharmacological treatment in slowing down OA progression, leading to costly surgical interventions eventually. Cell therapy using chondrocytes or progenitor cells from different sources has been reported in clinical trials for OA management with some success, but outcomes are varied. Peripheral blood derived mesenchymal stem cells (PB-MSCs) are promising cells owing to their easy collection, superior migration, and differentiation potentials. In the current study, we evaluated the effect of intra-articular administration of PB-MSCs on the progression of OA in mice.Methods: C57BL/6J mice (8-10 weeks old male) were subjected to destabilization of the medial meniscus surgeries (DMM) on their right joints following protocols as previously reported. The mice after DMM were randomly treated with saline (vehicle control), PB-MSCs, or adipose tissue derived MSCs (AD-MSCs) (n = 7 per group). The mice treated with sham surgery were regarded as sham controls (n = 7). PB-MSCs and AD-MSCs were harvested and cultured according to previous published protocols, and pre-labeled with BrdU for 48 h before use. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3~5) were injected into the right knee joints thrice post-surgery (except sham surgery group). The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations.Results: PB-MSCs administration significantly reduced hardening of subchondral bone comparing to vehicle controls. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which is comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of PB-MSCs-treated groups comparing to vehicle controls. Co-expression of BrdU and Sox9 were detected, indicating injected PB-MSCs differentiated towards chondrocytes in situ. Reduced level of IL-6 in the peripheral sera of PB-MSCs- and AD-MSCs-treated mice was also determined. Conclusions: Repetitive administration of PB-MSCs or AD-MSCs halted OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs may become a promising cell source for cartilage tissue repair and alleviation of OA progression.

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.

High Fibular Osteotomy Ameliorates Medial Compartment Knee Osteoarthritis in a Rabbit Model

2021 ◽  
Author(s):  
Feihua Yan ◽  
Xujun Zhao ◽  
Shisheng Duan ◽  
Aini Maimaiti ◽  
Yong Qi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Knee Osteoarthritis ◽  
Bone Remodeling ◽  
Western Blotting ◽  
Subchondral Bone ◽  
Rabbit Model ◽  
Medial Compartment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fibular Osteotomy ◽  
Tnf Α

Abstract Purpose Knee osteoarthritis (KOA) is a common and severe disease characterized by articular cartilage degeneration, subchondral bone remodeling and inflammation. This study aimed to investigate the therapeutic effects of high fibular osteotomy (HFO) in a KOA rabbit model and to examine the molecular mechanisms involved in medial compartment KOA protective effects.Methods A rabbit model of destabilization of the medial meniscus was used to induce post-traumatic KOA. The effectiveness of HFO on protection against KOA was tested. Hematoxylin and eosin staining, Safranin O/Fast green staining and micro-CT analysis were performed to evaluate structural and morphological changes. The expression of metalloproteinase (MMP)-1, MMP-3, MMP-13, collagen type II (Col2), a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)-5, aggrecan, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was assessed by real time PCR, western blotting and enzyme-linked immunosorbent assay. Additionally, western blotting was performed to test the expression of NFκB p65, phospho-IκBα and IκBα. Results HFO delayed the progression of articular cartilage damage and suppressed subchondral bone remodeling. HFO also decreased MMP-1, MMP-3, MMP-13 and ADAMTS-5 expression, and increased Col2 and aggrecan expression. In parallel, HFO attenuated the expression of IL-1β, IL-6 and TNF-α. Furthermore, the molecular mechanism underlying the protective effect of HFO in medial compartment KOA was related to the NFκB signaling pathway. Conclusion HFO may be a novel therapeutic approach to treating medial compartment KOA.

Quantitative study of articular cartilage and subchondral bone remodeling in the knee joint of dogs after strenuous running training

1992 ◽  
Vol 7 (S2) ◽  
pp. S419-S424 ◽  
Author(s):  
Ralf Oettmeier ◽  
Jari Arokoski ◽  
Andreas J. Roth ◽  
Heikki J. Helminen ◽  
Markky Tammi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Knee Joint ◽  
Bone Remodeling ◽  
Quantitative Study ◽  
Subchondral Bone ◽  
Running Training

scholarly journals Characterization of OA development between sexes in the rat medial meniscal transection model

2019 ◽  
Author(s):  
Krishna A. Pucha ◽  
Jay M. McKinney ◽  
Julia M. Fuller ◽  
Nick J. Willett
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Bone Structure ◽  
Meniscal Tear ◽  
Cartilage Degradation ◽  
Mineral Density ◽  
Male And Female ◽  
Post Surgery ◽  
Medial Meniscal Tear

AbstractObjectiveOsteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While there are clear sex differences in OA development in humans, most pre-clinical research has been conducted solely in male animals thus limiting the ability of these findings to be generalized to both sexes in the context of this disease. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical animal model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery.DesignA MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure.ResultsQuantitative analysis of the medial 1/3 articular cartilage via EPIC-μCT showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Additionally, both male and female animals in the MMT group had increased subchondral bone mineral density and larger total osteophyte volumes due to MMT.ConclusionThese data demonstrate that OA can be induced in both sexes using the rat MMT model. Moving forward, adding sex as a factor in preclinical OA studies should be standard practice in pre-clinical studies in order to elucidate more inclusive and translatable results into the clinic.

MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

2020 ◽  
Vol 99 (13) ◽  
pp. 1469-1477
Author(s):  
J.L. Sun ◽  
J.F. Yan ◽  
S.B. Yu ◽  
J. Zhao ◽  
Q.Q. Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Loss ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Volume Fraction ◽  
Cartilage Degradation ◽  
Specific Inhibition ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

Abnormal subchondral bone remodeling plays important roles during osteoarthritis (OA) pathology. Recent studies show that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones exhibit a prominent pro-osteoclastic effect that contributes to abnormal subchondral bone remodeling; however, the pathologic mechanism remains unclear. In the present study, we used a mouse model with OA-like change in the temporomandibular joint (TMJ) induced by an experimentally unilateral anterior crossbite (UAC) and found that the level of microRNA-29b ( miR-29b), but not miR-29a or miR-29c, was markedly lower in BMSCs from subchondral bones of UAC mice as compared with that from the sham control mice. With an intra-articular aptamer delivery system, BMSC-specific overexpression of miR-29b by aptamer-agomiR-29b rescued subchondral bone loss and osteoclast hyperfunction in UAC mice, as demonstrated by a significant increase in bone mineral density, bone volume fraction, trabecular thickness, and the gene expression of osteocalcin and Runx2 but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K, Trap, Wnt5a, Rankl, and Rank as compared with those in the UAC mice treated by aptamer-NC (all P < 0.05). In addition, BMSC-specific inhibition of miR-29b by aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affected miR-29b levels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression of miR-29b in UAC mice largely rescued OA-like cartilage degradation, including decreased chondrocyte density, cartilage thickness, and the percentage areas of proteoglycans and type II collagen, while BMSC-specific inhibition of miR-29b aggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identified Wnt5a, but not Rankl or Sdf-1, as the direct target of miR-29b. The results of the present study indicate that miR-29b is a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.

scholarly journals Osteoarthritis Early-, Mid- and Late-Stage Progression in the Rat Medial Meniscus Transection Model

2021 ◽  
Author(s):  
Thanh N. Doan ◽  
Jay M. McKinney ◽  
Krishna A Pucha ◽  
Fabrice C. Bernard ◽  
Nick J. Willett
Keyword(s):  
Articular Cartilage ◽  
Disease Progression ◽  
Subchondral Bone ◽  
Late Stage ◽  
Medial Meniscus ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Cell Therapies ◽  
Post Surgery ◽  
Established Disease

AbstractOsteoarthritis is a degenerative disease of synovial joints affecting all tissues, including the articular cartilage and underlying subchondral bone. Osteoarthritis animal models can recapitulate aspects of human disease progression and are commonly used to test the development of drugs, biomaterials, and cell therapies for treatment. The rat medial meniscus transection (MMT) model is a surgically induced post-traumatic osteoarthritis model and is one of the most commonly used models for therapeutic development; however, it is typically used to evaluate the efficacy of therapies to prevent disease development rather than testing the treatment of disease progression in already established disease. We describe herein, the qualitative and quantitative changes to articular cartilage, subchondral bone, and formation of osteophytes in rats at early-(3-weeks post-surgery), mid-(6-weeks post-surgery) and late-(12-weeks post-surgery) stages of osteoarthritis progression. Tibiae of MMT-operated animals showed loss of proteoglycan and fibrillation formation on articular cartilage surfaces as early as 3-weeks post-surgery. Using a contrast-enhanced μCT technique, quantitative, 3-dimensional analysis of the tibiae showed that the articular cartilage initially thickened at 3- and 6-weeks post-surgery and then decreased at 12-weeks post-surgery. This decrease in cartilage thickness corresponded with increased lesions in the articular cartilage, including fully degraded surfaces down to the subchondral bone layer. In this rat MMT model, subchondral bone thickening was significant at 6-weeks post-surgery and seem to follow cartilage damage. Osteophytes were found at 3-weeks post-surgery, which coincided with articular cartilage degradation. Cartilaginous osteophytes preceded mineralization suggesting that these marginal tissue growths most likely occurred through endochondral ossification. The use of the rat MMT model has predominantly been used out to 3-weeks, and most studies determine the effect of therapies to delay or prevent the onset of osteoarthritis. We provide evidence that an extension of the rat MMT model out to 6 and 12 weeks resembled more severe phenotypes of human osteoarthritis. The mid- to late-stages of rat MMT model can be used to evaluate the therapeutic efficacy of novel treatments to treat the progression of established disease — since patients typically present in the clinic when the disease is established and becomes symptomatic, thus evaluating the efficacy of new treatments at the late stage will be important for eventual clinical translation.

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