scholarly journals SOST Deficiency Aggravates Osteoarthritis in Mice by Promoting Sclerosis of Subchondral Bone

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Jingyu Li ◽  
Junjie Xue ◽  
Yan Jing ◽  
Manyi Wang ◽  
Rui Shu ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Cruciate Ligament ◽  
Cartilage Degradation ◽  
Cell Number ◽  
Blue Staining ◽  
Sham Operation ◽  
Knee Oa ◽  
Sost Gene ◽  
Bone Sclerosis ◽  
The Difference

As the initial part in the development of osteoarthritis (OA), subchondral bone sclerosis has been considered to be initiated by excess mechanical loading and proven to be correlated to other pathological changes. Sclerostin, which is an essential mechanical stress response protein, is encoded by the SOST gene. It is expressed in osteocytes and mature chondrocytes and has been proven to be closely correlated to OA. However, the relationship and mechanism between the SOST gene and the development of OA remain unclear. The aim of the present study was to investigate the role of the SOST gene in OA pathogenesis in the subchondral bone. A knee anterior cruciate ligament transection (ACLT) mouse osteoarthritis (OA) model on SOST-knockout (SOST KO) and wild-type (WT) mice was established. The pathogenic and phenotypic changes in the subchondral bone were investigated by histology, micro-CT, immunohistochemistry, TRAP staining, Masson staining, and Toluidine blue staining. It was found that sclerostin expression decreased in both the calcified cartilage and mineralized subchondral structures during the development of OA. Joint instability induced a severe cartilage degradation phenotype, with higher OARSI scores in SOST KO mice, when compared to WT mice. SOST KO mice with OA exhibited a higher BMD and BV/TV ratio, as well as a higher rate of bone remodeling and TRAP-positive cell number, when compared to the WT counterparts, but the difference was not significant between the sham-operation groups. It was concluded that loss of sclerostin aggravates knee OA in mice by promoting subchondral bone sclerosis and increasing catabolic activity of cartilage.

Finite Element Modelling of In Vitro Articular Cartilage Wear in the Patellofemoral Joint

2012 ◽  
Author(s):  
Lingmin Li ◽  
Shantanu Patil ◽  
Nick Steklov ◽  
Won Bae ◽  
Darryl D. D’Lima ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cruciate Ligament ◽  
Computational Simulation ◽  
Knee Kinematics ◽  
Cartilage Degradation ◽  
Knee Oa ◽  
Cartilage Wear ◽  
Anterior Cruciate ◽  
A Site

The mechanism by which altered knee joint motions and loads (e.g., following anterior cruciate ligament (ACL) injury) contribute to the development of knee osteoarthritis (OA) is not well understood. One mechanobiological hypothesis is that articular cartilage degradation is initiated when altered knee kinematics increase loading on certain regions of the articular surfaces and decrease loading on other regions [1]. If homeostatic loading conditions vary from region to region, then load changes induced by altered kinematics could initiate cartilage degradation in a site-specific manner. This hypothesis is attractive from a computational simulation perspective since it is based on mechanical factors that lend themselves well to physical modeling. If computational simulations could predict the knee OA development process, then they could potentially be used to facilitate the design of new or improved treatments for the disease.

scholarly journals Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

2021 ◽  
Vol 12 ◽  
Author(s):  
Houfu Ling ◽  
Qinghe Zeng ◽  
Qinwen Ge ◽  
Jiali Chen ◽  
Wenhua Yuan ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Common Disease ◽  
Dependent Manner ◽  
Wild Type ◽  
Bone Sclerosis

Osteoarthritis (OA) is a common disease characterized by cartilage degeneration. In recent years much attention has been paid to Traditional Chinese Medicine (TCM) since its treatments have shown efficacy for ameliorating cartilage degradation with mild side effects. Osteoking is a TCM prescription that has long been used in OA treatment. However, the exact mechanism of Osteoking are not fully elucidated. In the current study, destabilization of the medial meniscus (DMM)-induced OA mice was introduced as a wild type animal model. After 8 weeks of administration of Osteoking, histomorphometry, OARSI scoring, gait analysis, micro-CT, and immunohistochemical staining for Col2, MMP-13, TGFβRII and pSmad-2 were conducted to evaluate the chondroprotective effects of Osteoking in vivo. Further in vitro experiments were then performed to detect the effect of Osteoking on chondrocytes. TGFβRIICol2ER transgenic mice were constructed and introduced in the current study to validate whether Osteoking exerts its anti-OA effects via the TGF-β signaling pathway. Results demonstrated that in wild type DMM mice, Osteoking ameliorated OA-phenotype including cartilage degradation, subchondral bone sclerosis, and gait abnormality. Col2, TGFβRII, and pSmad-2 expressions were also found to be up-regulated after Osteoking treatment, while MMP-13 was down-regulated. In vitro, the mRNA expression of MMP-13 and ADAMTS5 decreased and the mRNA expression of Aggrecan, COL2, and TGFβRII were up-regulated after the treatment of Osteoking in IL-1β treated chondrocytes. The additional treatment of SB505124 counteracted the positive impact of Osteoking on primary chondrocytes. In TGFβRIICol2ER mice, spontaneous OA-liked phenotype was observed and treatment of Osteoking failed to reverse the OA spontaneous progression. In conclusion, Osteoking ameliorates OA progression by decelerating cartilage degradation and alleviating subchondral bone sclerosis partly via the TGF-β signaling pathway.

Computational Simulation of Articular Cartilage Wear in the Patellofemoral Joint During In Vitro Testing

2010 ◽  
Author(s):  
Lingmin Li ◽  
Shantanu Patil ◽  
Nick Steklov ◽  
Won Bae ◽  
Michele Temple-Wong ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cruciate Ligament ◽  
Computational Simulation ◽  
Knee Kinematics ◽  
Cartilage Degradation ◽  
Knee Oa ◽  
Cartilage Wear ◽  
Anterior Cruciate ◽  
A Site

The mechanism by which altered knee joint motions and loads (e.g., following anterior cruciate ligament (ACL) injury) contribute to the development of knee osteoarthritis (OA) is not well understood. One mechanobiological hypothesis is that articular cartilage degradation is initiated when altered knee kinematics increase loading on certain regions of the articular surfaces and decrease loading on other regions [1,2]. If homeostatic loading conditions vary from region to region, then load changes induced by altered kinematics could initiate cartilage degradation in a site-specific manner. This hypothesis is attractive from a computational simulation perspective since it is based on mechanical factors that lend themselves well to physical modeling. If computational simulations could reproduce the knee OA development process, then they potentially could be used to facilitate the design of new or improved treatments for the disease.

scholarly journals Kartogenin prevents cartilage degradation and alleviates osteoarthritis progression in mice via the miR-146a/NRF2 axis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Mingzhuang Hou ◽  
Yijian Zhang ◽  
Xinfeng Zhou ◽  
Tao Liu ◽  
Huilin Yang ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Cartilage Matrix ◽  
Related Factor ◽  
Dependent Manner ◽  
Matrix Degradation ◽  
Protein Levels ◽  
Bone Sclerosis

AbstractOsteoarthritis (OA) is a common articular degenerative disease characterized by loss of cartilage matrix and subchondral bone sclerosis. Kartogenin (KGN) has been reported to improve chondrogenic differentiation of mesenchymal stem cells. However, the therapeutic effect of KGN on OA-induced cartilage degeneration was still unclear. This study aimed to explore the protective effects and underlying mechanisms of KGN on articular cartilage degradation using mice with post-traumatic OA. To mimic the in vivo arthritic environment, in vitro cultured chondrocytes were exposed to interleukin-1β (IL-1β). We found that KGN barely affected the cell proliferation of chondrocytes; however, KGN significantly enhanced the synthesis of cartilage matrix components such as type II collagen and aggrecan in a dose-dependent manner. Meanwhile, KGN markedly suppressed the expression of matrix degradation enzymes such as MMP13 and ADAMTS5. In vivo experiments showed that intra-articular administration of KGN ameliorated cartilage degeneration and inhibited subchondral bone sclerosis in an experimental OA mouse model. Molecular biology experiments revealed that KGN modulated intracellular reactive oxygen species in IL-1β-stimulated chondrocytes by up-regulating nuclear factor erythroid 2-related factor 2 (NRF2), while barely affecting its mRNA expression. Microarray analysis further revealed that IL-1β significantly up-regulated miR-146a that played a critical role in regulating the protein levels of NRF2. KGN treatment showed a strong inhibitory effect on the expression of miR-146a in IL-1β-stimulated chondrocytes. Over-expression of miR-146a abolished the anti-arthritic effects of KGN not only by down-regulating the protein levels of NRF2 but also by up-regulating the expression of matrix degradation enzymes. Our findings demonstrate, for the first time, that KGN exerts anti-arthritic effects via activation of the miR-146a-NRF2 axis and KGN is a promising heterocyclic molecule to prevent OA-induced cartilage degeneration.

scholarly journals Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 990 ◽  
Author(s):  
Gundula Schulze-Tanzil
Keyword(s):  
Subchondral Bone ◽  
Transforming Growth Factor ◽  
Cruciate Ligament ◽  
Bone Destruction ◽  
Stem Cell Differentiation ◽  
Cyst Formation ◽  
Cartilage Degradation ◽  
Cellular Level ◽  
Bone Lesions ◽  
Joint Cartilage

Osteoarthritis (OA) induces inflammation and degeneration of all joint components including cartilage, joint capsule, bone and bone marrow, and ligaments. Particularly intraarticular ligaments, which connect the articulating bones such as the anterior cruciate ligament (ACL) and meniscotibial ligaments, fixing the fibrocartilaginous menisci to the tibial bone, are prone to the inflamed joint milieu in OA. However, the pathogenesis of ligament degeneration on the cellular level, most likely triggered by OA associated inflammation, remains poorly understood. Hence, this review sheds light into the intimate interrelation between ligament degeneration, synovitis, joint cartilage degradation, and dysbalanced subchondral bone remodeling. Various features of ligament degeneration accompanying joint cartilage degradation have been reported including chondroid metaplasia, cyst formation, heterotopic ossification, and mucoid and fatty degenerations. The entheses of ligaments, fixing ligaments to the subchondral bone, possibly influence the localization of subchondral bone lesions. The transforming growth factor (TGF)β/bone morphogenetic (BMP) pathway could present a link between degeneration of the osteochondral unit and ligaments with misrouted stem cell differentiation as one likely reason for ligament degeneration, but less studied pathways such as complement activation could also contribute to inflammation. Facilitation of OA progression by changed biomechanics of degenerated ligaments should be addressed in more detail in the future.

Radiographic Prevalence of Osteochondrosis in Yearling Feral Horses

1999 ◽  
Vol 12 (03) ◽  
pp. 151-155 ◽  
Author(s):  
L. W. Valentino ◽  
E. M. Gaughan ◽  
D. R. Biller ◽  
R. H. Raub ◽  
J. D. Lillich
Keyword(s):  
Subchondral Bone ◽  
Management Practices ◽  
Articular Surface ◽  
Radiographic Images ◽  
Feral Horses ◽  
Metacarpophalangeal Joints ◽  
Genetic Base ◽  
Domestic Horses ◽  
The Difference ◽  
Metatarsophalangeal Joints

The purpose of the study is to document the prevalence of articular surface osteochondrosis lesions in feral horses. Eighty yearling feral horses were used. Radiographic images of the left stifle, both tarsocrural, metatarsophalangeal, metacarpophalangeal joints were taken. Radiographs were examined for the presence of osteochondral fragmentation and abnormal outline of subchondral bone suggestive of osteochondrosis. The prevalence of each lesion was calculated for each joint as well as for overall prevalence within the group, the latter being 6.25%. Typical osteochondrosis lesions were found within the tarsocrural and metatarsophalangeal joints. Based on the difference in prevalence of osteochondrosis between feral and certain domestic horses, management practices and perhaps genetic base may have a greater influence on the development of the disease in horses than trauma alone.

scholarly journals Heterotopic ossification in the post cruciate ligament of the knee: a case report and literature review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cun Li ◽  
Zonggui Huang ◽  
K. C. Anil ◽  
Chendeng Lao ◽  
Qianghua Wu ◽  
...  
Keyword(s):  
Literature Review ◽  
Heterotopic Ossification ◽  
Knee Pain ◽  
Cruciate Ligament ◽  
Complete Recovery ◽  
X Rays ◽  
Related Factors ◽  
Knee Motion ◽  
Adequate Treatment ◽  
The Difference

Abstract Background Heterotopic ossification (HO) is noted most frequently in periarticular muscles and has not yet been reported in the cruciate ligaments of the knee. We present a rare case of symptomatic ossification of the posterior cruciate ligament (PCL). Case presentation A 59-year-old woman had a 2-year history of knee pain that was getting worse during knee motion and had restricted knee motion for 1 year. X-rays could not show the lesion clearly. Multi-planar computed tomography demonstrated ossification within the PCL with mild osteoarthritic changes and excluded any other intra-articular pathology. The patient underwent arthroscopic debridement and then experienced immediate relief of pain and complete recovery of range of motion. Conclusion This is the first report of HO in the PCL as a possible cause of knee pain and restricted knee motion. On the basis of literature review, this case elaborates the difference between HO and calcification in the ligaments, the related factors inducing HO and the undefined pathogenesis, and favorable prognosis after adequate treatment.

scholarly journals Follicle stimulating hormone and estradiol alter immune response in osteoarthritic mice in an opposite manner

2021 ◽  
Vol 35 ◽  
pp. 205873842110161
Author(s):  
Lyudmila Belenska-Todorova ◽  
Ralitsa Zhivkova ◽  
Maya Markova ◽  
Nina Ivanovska
Keyword(s):  
Follicle Stimulating Hormone ◽  
Endocrine System ◽  
Synovial Cell ◽  
Nuclear Factor Κb ◽  
Cartilage Degradation ◽  
Osteoclast Formation ◽  
Blue Staining ◽  
Serum Osteocalcin ◽  
Tnf Α ◽  
Stimulating Hormone

Although a number of studies have shown that the occurrence and progression of osteoarthritis (OA) is related to endocrine system dysfunction, there is limited evidence about what roles sex hormones play. The aim of the present study was to examine the capacity of 17β-estradiol (ED) and follicle stimulating hormone (FSH) to alter the differentiation of bone marrow (BM) cells in arthritic mice. The experiments were conducted in collagenase-induced osteoarthritis in mice. Cartilage degradation was observed by safranin and toluidine blue staining. Flow cytometry was used to define different BM and synovial cell populations. The influence of FSH and ED on osteoclastogenesis was studied in BM cultures and on the osteoblastogenesis in primary calvarial cultures. The levels of IL-8, TNF-α, FSH, and osteocalcin were estimated by ELISA. FSH increased cartilage degradation and serum osteocalcin levels, while ED abolished it and lowered serum osteocalcin. FSH elevated the percentage of monocytoid CD14+/RANK+ and B cell CD19+/RANK+ cells in contrast to ED which inhibited the accumulation of these osteogenic populations. Also, ED changed the percentage of CD105+/F4/80+ and CD11c+ cells in the synovium. FSH augmented and ED suppressed macrophage colony-stimulating factor (M-CSF) + receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast (OC) formation, and this correlated with a respective increase and decrease of IL-8 secretion. FSH did not influence osteoblast (OB) formation while ED enhanced this process in association with changes of TNF-α, IL-8, and osteocalcin production. ED reduced osteoclast generation in bone. The key outcome of the current study is that both hormones influenced BM cell differentiation, with FSH favoring osteoclast formation and ED favoring osteoblast accumulation.

scholarly journals Treadmill Exercise after Controlled Abnormal Joint Movement Inhibits Cartilage Degeneration and Synovitis

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 303
Author(s):  
Yuichiro Oka ◽  
Kenij Murata ◽  
Kaichi Ozone ◽  
Takuma Kano ◽  
Yuki Minegishi ◽  
...  
Keyword(s):  
Treadmill Exercise ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Therapeutic Effects ◽  
Joint Movement ◽  
Knee Oa ◽  
Anterior Cruciate ◽  
Safranin O ◽  
Walking Group

Cartilage degeneration is the main pathological component of knee osteoarthritis (OA), but no effective treatment for its control exists. Although exercise can inhibit OA, the abnormal joint movement with knee OA must be managed to perform exercise. Our aims were to determine how controlling abnormal joint movement and treadmill exercise can suppress cartilage degeneration, to analyze the tissues surrounding articular cartilage, and to clarify the effect of treatment. Twelve-week-old ICR mice (n = 24) underwent anterior cruciate ligament transection (ACL-T) surgery on their right knees and were divided into three groups as follows: ACL-T, animals in the walking group subjected to ACL-T; controlled abnormal joint movement (CAJM), and CAJM with exercise (CAJM + Ex) (n = 8/group). Walking-group animals were subjected to treadmill exercise 6 weeks after surgery, including walking for 18 m/min, 30 min/day, 3 days/week for 8 weeks. Safranin-O staining, hematoxylin-eosin staining, and immunohistochemical staining were performed. The OARSI (Osteoarthritis research Society international) score was lower in the CAJM group than in the ACL-T group and was even lower in the CAJM + Ex group. The CAJM group had a lower meniscal injury score than the ACL-T group, and the CAJM + Ex group demonstrated a less severe synovitis than the ACL-T and CAJM groups. The observed difference in the perichondrium tissue damage score depending on the intervention method suggests different therapeutic effects, that normalizing joint motion can solve local problems in the knee joint, and that the anti-inflammatory effect of treadmill exercise can suppress cartilage degeneration.

Sign in / Sign up

Export Citation Format

Share Document