scholarly journals Peptide-biofunctionalization of biomaterials for osteochondral tissue regeneration in early stage osteoarthritis: challenges and opportunities

2019 ◽  
Vol 7 (7) ◽  
pp. 1027-1044 ◽  
Author(s):  
D. Bicho ◽  
S. Ajami ◽  
C. Liu ◽  
R. L. Reis ◽  
J. M. Oliveira
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Tissue Regeneration ◽  
Early Stage ◽  
Degenerative Joint Disease ◽  
Synovial Inflammation ◽  
Joint Disease ◽  
Progressive Deterioration ◽  
Challenges And Opportunities ◽  
Osteochondral Tissue

Osteoarthritis is a degenerative joint disease characterized by the progressive deterioration of articular cartilage, synovial inflammation and changes in periarticular and subchondral bone, being a leading cause of disability.

scholarly journals Baicalein Alleviates Osteoarthritis Progression in Mice by Protecting Subchondral Bone and Suppressing Chondrocyte Apoptosis Based on Network Pharmacology

2022 ◽  
Vol 12 ◽  
Author(s):  
Nanxing Yi ◽  
Yilin Mi ◽  
Xiaotong Xu ◽  
Naping Li ◽  
Fan Zeng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Articular Cartilage ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Caspase 3 ◽  
Synovial Inflammation ◽  
Joint Disease ◽  
Network Pharmacology ◽  
Chondrocyte Apoptosis ◽  
Apoptotic Signaling

As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.

scholarly journals The Effects of Annatto Tocotrienol Supplementation on Cartilage and Subchondral Bone in an Animal Model of Osteoarthritis Induced by Monosodium Iodoacetate

2019 ◽  
Vol 16 (16) ◽  
pp. 2897 ◽  
Author(s):  
Kok-Yong Chin ◽  
Sok Kuan Wong ◽  
Fadhlullah Zuhair Japar Sidik ◽  
Juliana Abdul Hamid ◽  
Nurul Hafizah Abas ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Sham Group ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Sprague Dawley ◽  
Joint Protection ◽  
Sprague Dawley Rats ◽  
Monosodium Iodoacetate ◽  
Inflammatory Component

Osteoarthritis is a degenerative joint disease which primarily affects the articular cartilage and subchondral bones. Since there is an underlying localized inflammatory component in the pathogenesis of osteoarthritis, compounds like tocotrienol with anti-inflammatory properties may be able to retard its progression. This study aimed to determine the effects of oral tocotrienol supplementation on the articular cartilage and subchondral bone in a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). Thirty male Sprague-Dawley rats (three-month-old) were randomized into five groups. Four groups were induced with osteoarthritis (single injection of MIA at week 0) and another served as the sham group. Three of the four groups with osteoarthritis were supplemented with annatto tocotrienol at 50, 100 and 150 mg/kg/day orally for five weeks. At week 5, all rats were sacrificed, and their tibial-femoral joints were harvested for analysis. The results indicated that the groups which received annatto tocotrienol at 100 and 150 mg/kg/day had lower histological scores and cartilage remodeling markers. Annatto tocotrienol at 150 mg/kg/day significantly lowered the osteocalcin levels and osteoclast surface of subchondral bone. In conclusion, annatto tocotrienol may potentially retard the progression of osteoarthritis. Future studies to confirm its mechanism of joint protection should be performed.

scholarly journals Brachygnathia Superior and Degenerative Joint Disease: A New Lethal Syndrome in Angus Calves

1987 ◽  
Vol 24 (2) ◽  
pp. 148-155 ◽  
Author(s):  
M. Jayo ◽  
H. W. Leipold ◽  
S. M. Dennis ◽  
F. E. Eldridge
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Genetic Basis ◽  
Degenerative Joint Disease ◽  
Etiologic Agent ◽  
Joint Disease ◽  
Histochemical Analysis ◽  
Chondrocyte Proliferation ◽  
Histological Changes ◽  
Palatine Bone

Brachygnathia superior and generalized diarthrodial degenerative joint disease were seen in 17 related, purebred Angus calves ranging in age from 2 days to 4 months. Craniometrical studies revealed decreased maxillary and palatine bone lengths and increased cranial, skull, and facial indices. Radiological evaluation of major appendicular joints demonstrated lipping of the joint margins with osteophyte formation, sclerosis of subchondral bone, and narrowing of joint spaces. Synovial fluid evaluation indicated joint degeneration but no etiologic agent. Rheumatoid factor analysis of plasma was negative. Grossly, all major appendicular joints were defective including the atlanto-occipital articulation. Lesions ranged from loss of surface luster to erosions and deep ulcers with eburnation of the subchondral bone and secondary proliferative synovitis. Histological changes were degeneration of the articular cartilage matrix, chondrocyte necrosis, flaking and fibrillation, chondrone formation, erosions and ulcers of the articular cartilage with subchondral bone sclerosis, vascular invasion with fibrosis, and chronic, nonsuppurative, proliferative synovitis. Growth plates had defective chondrocyte proliferation and hypertrophy with aberrant ossification of calcified cartilaginous matrix. Histochemical analysis of cartilage and bone failed to incriminate which component was defective, glycosaminoglycan or collagen, but indicated different distribution or absence of one or the other. Genealogic studies revealed a genetic basis for the new defect.

scholarly journals Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8934 ◽  
Author(s):  
Yutao Yang ◽  
Peiran Li ◽  
Songsong Zhu ◽  
Ruiye Bi
Keyword(s):  
Subchondral Bone ◽  
Early Stage ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
The Elderly ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Bone Change ◽  
Subchondral Bone Change

Osteoarthritis (OA) is a chronic degenerative joint disease and the major cause of joint pain and disability in the elderly. It is mainly characterized by articular cartilage degradation and subchondral bone remodeling. There are two main types of OA: natural occurring OA and secondary OA, mainly associated with aging and trauma, respectively. In this study, we established two OA models in rat knee joints to simulate the two types of OA, using the type II collagenase injection (CI) and anterior cruciate ligament transection (ACLT), respectively. After intervention for 2–6 weeks, cartilage and subchondral bone changes were detected in histological staining, immunochemistry, and micro-CT. Results showed that both models with typical pathology changes of OA were successfully induced, while the development and severity of OA process in the models were different. In ACLT rats, the cartilage damage was milder, lasted for a shorter time, and subchondral bone reconstruction occurred earlier, compared with the changes in CI rats. The cartilage damage was secondary to subchondral bone change in ACLT rats, while subchondral bone change was secondary to cartilage degeneration in CI rats. In conclusion, the interaction between cartilage and subchondral bone is different between the natural-occurring and secondary OA models. These two models not only suggest potential different mechanisms of the two types of OA, but also provide new directions for OA treatment and prevention.

scholarly journals Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis

2020 ◽  
pp. annrheumdis-2020-218089
Author(s):  
Wenhui Hu ◽  
Yueqi Chen ◽  
Ce Dou ◽  
Shiwu Dong
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Bone Destruction ◽  
The Elderly ◽  
Cell Types ◽  
Degenerative Joint Disease ◽  
Cellular Level ◽  
Joint Disease ◽  
Cellular Interactions ◽  
Bone Microenvironment

Osteoarthritis (OA) is a degenerative joint disease in the elderly. Although OA has been considered as primarily a disease of the articular cartilage, the participation of subchondral bone in the pathogenesis of OA has attracted increasing attention. This review summarises the microstructural and histopathological changes in subchondral bone during OA progression that are due, at the cellular level, to changes in the interactions among osteocytes, osteoblasts, osteoclasts (OCs), endothelial cells and sensory neurons. Therefore, we focus on how pathological cellular interactions in the subchondral bone microenvironment promote subchondral bone destruction at different stages of OA progression. In addition, the limited amount of research on the communication between OCs in subchondral bone and chondrocytes (CCs) in articular cartilage during OA progression is reviewed. We propose the concept of ‘OC–CC crosstalk’ and describe the various pathways by which the two cell types might interact. Based on the ‘OC–CC crosstalk’, we elaborate potential therapeutic strategies for the treatment of OA, including restoring abnormal subchondral bone remodelling and blocking the bridge—subchondral type H vessels. Finally, the review summarises the current understanding of how the subchondral bone microenvironment is related to OA pain and describes potential interventions to reduce OA pain by targeting the subchondral bone microenvironment.

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 Effects of chondroitin sulfate and sodium hyaluronate on chondrocytes and extracellular matrix of articular cartilage in dogs with degenerative joint disease

2008 ◽  
Vol 60 (1) ◽  
pp. 93-102 ◽  
Author(s):  
G. Gonçalves ◽  
E.G. Melo ◽  
M.G. Gomes ◽  
V.A. Nunes ◽  
C.M.F. Rezende
Keyword(s):  
Articular Cartilage ◽  
Chondroitin Sulfate ◽  
Sodium Hyaluronate ◽  
Nucleolar Organizer ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Control Group ◽  
Nucleolar Organizer Regions ◽  
Morphological Evaluation ◽  
Cell Counts

Samples of articular cartilage of femur, tibia and patella of 15 dogs with experimentally induced degenerative joint disease (DJD) were microscopically analyzed. Animals were distributed into three groups (n=5): the control group received no medication; the second group was treated with chondroitin sulfate and the third received sodium hyaluronate. Samples were processed and stained with HE and toluidine blue for morphological evaluation. The metabolic and proliferative activity of the chondrocytes was evaluated by the measurement of nucleolar organizer regions (NORs) after impregnation by silver nitrate. Significant differences were not observed (P>0.05) in the morphology among the groups, however, the group treated with sodium hyaluronate had a higher score suggesting a trend to a greater severity of the lesions. Significant differences were not observed (P>0.05) in the measurement of NORs, cells and NORs/cells among the groups. Although differences were not significant, sodium hyaluronate group showed higher NOR and cell counts which suggested an increase of the proliferation rate of chondrocytes. In addition, a higher NOR/cell ratio in the group treated with chondroitin sulfate suggested that this drug may have stimulated the metabolic activity of the chondrocytes, minimizing the lesions resulting from DJD.

scholarly journals New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 637 ◽  
Author(s):  
Paula Carpintero-Fernandez ◽  
Marta Varela-Eirin ◽  
Alessandra Lacetera ◽  
Raquel Gago-Fuentes ◽  
Eduardo Fonseca ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Molecular Model ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Novel Therapy ◽  
Human Cartilage ◽  
Sialic Acid Receptors ◽  
Cartilage Breakdown

Osteoarthritis (OA) is the most common degenerative joint disease characterized by articular cartilage degradation and joint degeneration. The articular cartilage is mainly formed by chondrocytes and a collagen-proteoglycan extracellular matrix that contains high levels of glycosylated proteins. It was reported that the shift from glycoproteins containing α-2,6-linked sialic acids to those that contain α-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of α-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the α-2,3-sialylated transmembrane mucin receptor, known as podoplanin (PDPN). Additionally, the Maackia amurensis seed lectin (MASL), that can be utilized to target PDPN, attenuates the inflammatory response mediated by NF-kB activation in primary chondrocytes and protects human cartilage breakdown ex vivo and in an animal model of arthritis. These findings reveal that specific lectins targeting α-2,3-sialylated receptors on chondrocytes might effectively inhibit cartilage breakdown. We also present a computational 3D molecular model for this interaction. These findings provide mechanistic information on how a specific lectin could be used as a novel therapy to treat degenerative joint diseases such as osteoarthritis.

A CURRENT REVIEW ON THE BIOLOGY AND TREATMENT OF ARTICULAR CARTILAGE DEFECTS (PART I & PART II)

2003 ◽  
Vol 07 (03n04) ◽  
pp. 157-181 ◽  
Author(s):  
Craig Willers ◽  
David J. Wood ◽  
Ming H. Zheng
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
18Th Century ◽  
Later Life ◽  
Fibrin Clot ◽  
Joint Disease ◽  
Cartilage Defects ◽  
Adult Males ◽  
Chondrocyte Implantation ◽  
Osteochondral Injury

Osteochondral injury occurs predominantly in physically active young adult males. Injury to the articular cartilage and/or subchondral bone may not only cause acute joint disease resulting in osseous intracapsular (synovitis) or extracapsular pain, but may also act to spawn arthritic conditions in later life. Since the 18th century, such injury has proven difficult to treat clinically, and much therapy has been essentially palliative. Past treatments such as abrasion arthroplasty, drilling, microfracture and arthroscopic lavage have been useful in removing articular debris and promoting the formation of the fibrin clot used in most native repair mechanisms. However, the limitation of these techniques is their inability to restore the damaged cartilage and subchondral bone to their normal tissue architecture. Recent developments in tissue engineering have concentrated on the utilization of autologous chondrocyte implantation, biomaterials and growth factors to promote the regeneration of biomechanically superior hyaline articular cartilage. This paper reviews the etiology, repair biology and therapeutic techniques of cartilage and/or osteochondral injury over the previous decades, and attempts to provide insight into interesting new research directions which offer much potential for improved treatment of these troublesome lesions.

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