In vivo effect of the Chinese Tenghuang Jiangu formula on cartilage destruction and subchondral 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.

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Subchondral bone sclerosis in the DMM model of murine OA is not associated with changes in either BMD or nanomechanical properties

Bone Abstracts ◽

10.1530/boneabs.3.pp20 ◽

2014 ◽

Author(s):

Patricia Das Neves Borges ◽

Tonia L Vincent ◽

Michelle L Oyen ◽

Massimo Marenzana

Keyword(s):

Subchondral Bone ◽

Nanomechanical Properties ◽

Bone Sclerosis

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Faculty Opinions recommendation of Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic knees.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.4998958.4932057 ◽

2010 ◽

Author(s):

Mark Johnson ◽

Cielo Barragan

Keyword(s):

Subchondral Bone ◽

Cartilage Destruction ◽

Chondrocyte Apoptosis

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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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Potential Implantable Nanofibrous Biomaterials Combined with Stem Cells for Subchondral Bone Regeneration

Materials ◽

10.3390/ma13143087 ◽

2020 ◽

Vol 13 (14) ◽

pp. 3087

Author(s):

Rana Smaida ◽

Luc Pijnenburg ◽

Silvia Irusta ◽

Erico Himawan ◽

Gracia Mendoza ◽

...

Keyword(s):

Stem Cells ◽

Bone Regeneration ◽

Subchondral Bone ◽

Therapeutic Potential ◽

Sodium Hyaluronate ◽

Vinyl Pyrrolidone ◽

Regenerative Ability ◽

Poly Vinyl Pyrrolidone

The treatment of osteochondral defects remains a challenge. Four scaffolds were produced using Food and Drug Administration (FDA)-approved polymers to investigate their therapeutic potential for the regeneration of the osteochondral unit. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) scaffolds were made by electrohydrodynamic techniques. Hydroxyapatite (HAp) and/or sodium hyaluronate (HA) can be then loaded to PCL nanofibers and/or PVP particles. The purpose of adding hydroxyapatite and sodium hyaluronate into PCL/PVP scaffolds is to increase the regenerative ability for subchondral bone and joint cartilage, respectively. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were seeded on these biomaterials. The biocompatibility of these biomaterials in vitro and in vivo, as well as their potential to support MSC differentiation under specific chondrogenic or osteogenic conditions, were evaluated. We show here that hBM-MSCs could proliferate and differentiate both in vitro and in vivo on these biomaterials. In addition, the PCL-HAp could effectively increase the mineralization and induce the differentiation of MSCs into osteoblasts in an osteogenic condition. These results indicate that PCL-HAp biomaterials combined with MSCs could be a beneficial candidate for subchondral bone regeneration.

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119 CHARACTERISATION OF TEMPORAL SUBCHONDRAL BONE CHANGES IN A RAT MODEL OF LOW-DOSE MONOSODIUM IODOACETATE INDUCED OSTEOARTHRITIS: AN IN VIVO MICRO-CT STUDY

Osteoarthritis and Cartilage ◽

10.1016/s1063-4584(11)60146-5 ◽

2011 ◽

Vol 19 ◽

pp. S61-S62 ◽

Cited By ~ 1

Author(s):

G. Mohan ◽

E. Perilli ◽

J. Kuliwaba ◽

I. Parkinson ◽

J. Humphries ◽

...

Keyword(s):

Subchondral Bone ◽

Rat Model ◽

Low Dose ◽

Micro Ct ◽

Bone Changes ◽

Monosodium Iodoacetate

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Tissue Modification of the Lateral Compartment of the Tibio-Femoral Joint Following In Vivo Varus Loading in the Rat

Journal of Biomechanical Engineering ◽

10.1115/1.4007453 ◽

2012 ◽

Vol 134 (10) ◽

Cited By ~ 4

Author(s):

M. L. Roemhildt ◽

B. D. Beynnon ◽

M. Gardner-Morse ◽

K. Anderson ◽

G. J. Badger

Keyword(s):

Articular Cartilage ◽

Subchondral Bone ◽

Compressive Loading ◽

Compressive Load ◽

Lateral Compartment ◽

Peripheral Region ◽

Degenerative Changes ◽

Medial Compartment ◽

Compressive Loads

This study describes the first application of a varus loading device (VLD) to the rat hind limb to study the role of sustained altered compressive loading and its relationship to the initiation of degenerative changes to the tibio-femoral joint. The VLD applies decreased compressive load to the lateral compartment and increased compressive load to the medial compartment of the tibio-femoral joint in a controlled manner. Mature rats were randomized into one of three groups: unoperated control, 0% (sham), or 80% body weight (BW). Devices were attached to an animal’s leg to deliver altered loads of 0% and 80% BW to the experimental knee for 12 weeks. Compartment-specific material properties of the tibial cartilage and subchondral bone were determined using indentation tests. Articular cartilage, calcified cartilage, and subchondral bone thicknesses, articular cartilage cellularity, and degeneration score were determined histologically. Joint tissues were sensitive to 12 weeks of decreased compressive loading in the lateral compartment with articular cartilage thickness decreased in the peripheral region, subchondral bone thickness increased, and cellularity of the midline region decreased in the 80% BW group as compared to the 0% BW group. The medial compartment revealed trends for diminished cellularity and aggregate modulus with increased loading. The rat-VLD model provides a new system to evaluate altered quantified levels of chronic in vivo loading without disruption of the joint capsule while maintaining full use of the knee. These results reveal a greater sensitivity of tissue parameters to decreased loading versus increased loading of 80% BW for 12 weeks in the rat. This model will allow future mechanistic studies that focus on the initiation and progression of degenerative changes with increased exposure in both magnitude and time to altered compressive loads.

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SAT0060 Proteomic analysis of osteoblasts secretome provides new insights in mechanisms underlying osteoarthritis subchondral bone sclerosis

10.1136/annrheumdis-2018-eular.1028 ◽

2018 ◽

Author(s):

C. Sanchez ◽

G. Mazzucchelli ◽

F. Comblain ◽

C. Lambert ◽

E. DePauw ◽

...

Keyword(s):

Subchondral Bone ◽

Proteomic Analysis ◽

Bone Sclerosis

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Selective STAT3 Inhibitor Alantolactone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.730312 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenbin Pei ◽

Xiaojian Huang ◽

Bowei Ni ◽

Rui Zhang ◽

Guangyi Niu ◽

...

Keyword(s):

Western Blot ◽

Inflammatory Responses ◽

Cartilage Degeneration ◽

Cartilage Destruction ◽

Signaling Molecules ◽

Inflammatory Factors ◽

Signal Pathways ◽

Autophagic Flux ◽

Safranin O

Osteoarthritis (OA), which is identified by chronic pain, impacts the quality of life. Cartilage degradation and inflammation are the most relevant aspects involved in its development. Signal transducer and activator of transcription 3(STAT3), a member of the STATs protein family, is associated with inflammation. Alantolactone (ALT), a sesquiterpene lactone compound, can selectively suppress the phosphorylation of STAT3. However, the pharmacological effect of ALT on OA is still imprecise. In this study, IL-1β (10 ng/ml) was applied to cartilage chondrocytes, which were treated with different concentrations of Alantolactone for 24 h. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX2), matrix metalloproteinases (MMPs) and thrombospondin motifs-5 (ADAMTS5) were detected by western blot. Protein expression of Collagen Ⅱ was observed by western blot, safranin O staining and immunofluorescence. Manifestation of autophagy related proteins such as autophagy-related gene-5 (ATG5), P62, LC3Ⅱ/Ⅰ and PI3K/AKT/mTOR-related signaling molecules were measured by western blot and autophagic flux monitored by confocal microscopy. Expression of STAT3 and NF-κB-related signaling molecules were evaluated by western blot and immunofluorescence. In vivo, 2 mg/kg ALT or equal bulk of vehicle was engaged in the destabilization of medial meniscus (DMM) mouse models by intra-articular injection, the degree of cartilage destruction was classified by Safranin O/Fast green staining. Our findings reported that the enhance of inflammatory factors containing iNOS, COX2, MMPs and ADAMTS5 induced by IL-1β could be ameliorated by ALT. Additionally, the diminish of Collagen Ⅱ and autophagy which was stimulated by IL-1β could be alleviated by ALT. Mechanistically, STAT3, NF-κB and PI3K/AKT/mTOR signal pathways might be involved in the effect of ALT on IL-1β-induced mouse chondrocytes. In vivo, ALT protected cartilage in the DMM mouse model. Overall, this study illustrated that ALT attenuated IL-1β-induced inflammatory responses, relieved cartilage degeneration and promoted impaired autophagy via restraining of STAT3 and NF-κB signal pathways, implying its auspicious therapeutical effect for OA.

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