Osteoclasts are recruited to the subchondral bone in naturally occurring post-traumatic equine carpal osteoarthritis and may contribute to cartilage degradation

Examination of the term stress in naturally occurring vernacular prose provides evidence of three separate senses being conflated. A corpus analysis of 818 instances of stress from non-academic texts in the Corpus of Contemporary American English (COCA) and the Corpus of American Discourses on Health (CADOH) shows a negative prosody for stress, which is portrayed variously as a source outside the body, a physical symptom within the body and an emotional state. The data show that contemporary speakers intermingle the three senses, making more difficult a discussion between doctors and patients of ways to ‘reduce stress’, when stress might be interpreted as a stressor, a symptom, or state of anxiety. This conflation of senses reinforces the impression that stress is pervasive and increasing. In addition, a semantic shift is also refining a new sense for stress, as post-traumatic stress develops as a specific subtype of emotional stress whose use has increased in circulation in the past 20 years.

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

Applied Sciences ◽

10.3390/app11157118 ◽

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.

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

Journal of Bone and Mineral Research ◽

10.1002/jbmr.4397 ◽

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

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

BioMed Research International ◽

10.1155/2019/7623562 ◽

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.

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

10.21203/rs.3.rs-910616/v1 ◽

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.

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

Cells ◽

10.3390/cells9040927 ◽

2020 ◽

Vol 9 (4) ◽

pp. 927 ◽

Cited By ~ 5

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.

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

Arthritis Research & Therapy ◽

10.1186/s13075-020-02374-x ◽

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.

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DEVELOPING THE COMMON MARMOSET AS A TRANSLATIONAL MODEL OF AGE-RELATED OSTEOARTHRITIS

Innovation in Aging ◽

10.1093/geroni/igz038.390 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S104-S104

Author(s):

Dennis M Minton ◽

Angela J Marolf ◽

Kelly S Santangelo ◽

Adam B Salmon ◽

Adam R Konopka

Keyword(s):

Subchondral Bone ◽

Bone Structure ◽

Common Marmoset ◽

Knee Joints ◽

Micro Computed Tomography ◽

Bone Thickness ◽

Aging Research ◽

Naturally Occurring ◽

Age Related ◽

The Common

Abstract Age is a primary risk factor for osteoarthritis (OA). The mechanisms that contribute to OA are poorly understood and disease modifying treatments have not been identified. A critical shortcoming in developing therapies is the limited number of translational models available to identify the causes of naturally occurring OA. Our goal is to use the common marmoset as a non-human primate (NHP) model of age-related OA. NHP are the closest evolutionary relative to humans and share many characteristics of human aging. The marmoset has advantages over other NHP for aging research because of their relatively short maximal lifespan and small size. Micro-computed tomography (uCT) was performed on whole-knee joints obtained from young (10 yrs, n=3) marmosets at necropsy. OA was evaluated using a clinical uCT scoring system and quantitative assessments of subchondral bone structure and ossified meniscal volume. Advancing age was positively correlated to increased uCT OA score (p<0.05, r=0.59 ), mainly through increased number and size of osteophytes and progressive subchondral bone sclerosis from the medial to both medial and lateral compartments. For marmosets displaying meniscal ossification, older marmosets had greater (p<0.05) ossified meniscal volume than middle-aged and younger marmosets, respectively. Trabecular (p=0.05) and cortical bone thickness (p<0.05) were also lower in older marmosets. These data are the first to indicate that the marmoset develops naturally occurring, age-related OA and support the pursuit of additional studies using the marmoset to identify OA mechanisms and test potential interventions.

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