Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats

Bone ◽  
2011 ◽  
Vol 48 (2) ◽  
pp. 362-371 ◽  
Author(s):  
Kai Jiao ◽  
Li-Na Niu ◽  
Mei-Qing Wang ◽  
Juan Dai ◽  
Shi-Bin Yu ◽  
...  
Keyword(s):  
Bone Loss ◽  
Subchondral Bone ◽  
Cartilage Degradation

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 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.

scholarly journals Pirfenidone reduces subchondral bone loss and fibrosis after murine knee cartilage injury

2017 ◽  
Author(s):  
Deva D. Chan ◽  
Jun Li ◽  
Wei Luo ◽  
Dan N. Predescu ◽  
Brian J. Cole ◽  
...  
Keyword(s):  
Bone Loss ◽  
Subchondral Bone ◽  
Cartilage Injury ◽  
Knee Cartilage

scholarly journals Pregnancy and Lactation Impair Subchondral Bone Leading to Reduced Rat Supraspinatus Tendon-to-Bone Insertion Site Failure Properties

2020 ◽  
Vol 142 (11) ◽  
Author(s):  
Ashley K. Fung ◽  
Snehal S. Shetye ◽  
Yihan Li ◽  
Yilu Zhou ◽  
X. Sherry Liu ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Loss ◽  
Subchondral Bone ◽  
Bone Mineralization ◽  
Insertion Site ◽  
Supraspinatus Tendon ◽  
Bone Microstructure ◽  
Female Rats ◽  
Pregnancy And Lactation ◽  
Failure Properties

Abstract Pregnant women experience weight gain, gait changes, and biochemical fluctuations that impair joint function and alter the maternal skeleton. Hormonal changes increase pelvic ligament laxity in preparation for childbirth and affect peripheral joint laxity. Calcium demands also rise during pregnancy and lactation, resulting in reduced bone mineral density (BMD) and maternal bone loss. Altered tendon properties and bone loss during pregnancy and lactation may impact tendon insertion sites, such as rotator cuff tendons where insertion site ruptures are common. However, the effects of pregnancy and lactation at the tendon-to-bone interface have not been investigated. Therefore, the objective of this study was to evaluate supraspinatus tendon mechanical properties and insertion site microstructure during pregnancy, lactation, and postweaning recovery in female rats. We hypothesized that pregnancy and lactation would compromise supraspinatus tendon mechanical properties and subchondral bone microstructure. Female rats were divided into virgin, pregnancy, lactation, and recovery groups, and supraspinatus tendons were mechanically evaluated. Surprisingly, tendon mechanics was unaffected by pregnancy and lactation. However, tendon modulus decreased two-weeks postweaning. Additionally, tendons failed by bony avulsion at the insertion site, and the lactation group exhibited reduced failure properties corresponding to decreased subchondral bone mineralization. Lactation also resulted in dramatic bone loss at the epiphysis, but trabecular bone microarchitecture recovered postweaning. In conclusion, lactation following pregnancy impaired trabecular bone microstructure and subchondral bone mineralization, leading to reduced supraspinatus tendon-to-bone insertion site failure properties. These findings will contribute toward understanding the pathogenesis of tendon-to-bone disorders.

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 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.

Doxycycline effects on mechanical and morphometrical properties of early- and late-stage osteoarthritic bone following anterior cruciate ligament injury

2004 ◽  
Vol 97 (4) ◽  
pp. 1254-1260 ◽  
Author(s):  
Connor K. Pardy ◽  
John R. Matyas ◽  
Ronald F. Zernicke
Keyword(s):  
Anterior Cruciate Ligament ◽  
Bone Loss ◽  
Trabecular Bone ◽  
Subchondral Bone ◽  
Bone Structure ◽  
Femoral Condyle ◽  
Cruciate Ligament ◽  
Ligament Injury ◽  
Doxycycline Treatment ◽  
Anterior Cruciate

As posttraumatic osteoarthritis (OA) progresses, the mechanical and morphometrical properties of the subchondral bone change and may be linked to damage of the articular cartilage. Potentially to slow that progression, doxycycline was administered orally twice daily (4 mg·kg−1·day−1) in skeletally mature canines after anterior cruciate ligament transection (ACLX). To test if doxycycline significantly altered the structure and function of OA bone, we tested cancellous bone mechanical properties, measured bone mineral content, and analyzed bone structure by microcomputed tomography. Our investigation focused on subchondral trabecular bone changes in the medial femoral condyle at 36 and 72 wk after ACLX. Significant mechanical changes discovered at 36 wk post-ACLX were less obvious at 72 wk in both treated and ACLX groups. Doxycycline treatment conserved bone strain energy density at 72 wk. Doxycycline had little effect on the degradation of superficial osseous tissue at 36 wk post-ACLX; by 72 wk, doxycycline in an ACLX model limited subchondral bone loss within the first 3 mm of periarticular bone with established OA. Significant bone loss occurred in the deeper trabecular bone for all groups. Substantial architectural adaptation within deeper trabecular bone accompanied changes in mechanics in early and established OA.

scholarly journals Protease-activated receptor 2: a novel pathogenic pathway in a murine model of osteoarthritis

2010 ◽  
Vol 69 (11) ◽  
pp. 2051-2054 ◽  
Author(s):  
William R Ferrell ◽  
Elizabeth B Kelso ◽  
John C Lockhart ◽  
Robin Plevin ◽  
Iain B McInnes
Keyword(s):  
Bone Formation ◽  
Subchondral Bone ◽  
Therapeutic Target ◽  
Cartilage Degradation ◽  
Wild Type ◽  
Potential Therapeutic Target ◽  
Cartilage Erosion ◽  
Protease Activated Receptor 2 ◽  
Deficient Mice

ObjectiveOsteoarthritis is a global clinical challenge for which no effective disease-modifying agents currently exist. This study identified protease-activated receptor 2 (PAR-2) as a novel pathogenic mechanism and potential therapeutic target in osteoarthritis.MethodsExperimental osteoarthritis was induced in wild-type and PAR-2-deficient mice by sectioning the medial meniscotibial ligament (MMTL), leading to the development of a mild arthropathy. Cartilage degradation and increased subchondral bone formation were assessed as indicators of osteoarthritis pathology.ResultsFour weeks following MMTL section, cartilage erosion and increased subchondral bone formation was evident in wild-type mice but was substantially reduced in PAR-2-deficient mice. Crucially, the therapeutic inhibition of PAR-2 in wild-type mice, using either a PAR-2 antagonist or a monoclonal antibody targeting the protease cleavage site of PAR-2, was also equally effective at reducing osteoarthritis progression in vivo. PAR-2 was upregulated in chondrocytes of wild-type but not sham-operated mice. Wild-type mice showed further joint degradation 8 weeks after the induction of osteoarthritis, but PAR-2-deficient mice were still protected.ConclusionsThe substantial protection from pathology afforded by PAR-2 deficiency following the induction of osteoarthritis provides proof of concept that PAR-2 plays a key role in osteoarthritis and suggests this receptor as a potential therapeutic target.

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