Cartilage Degeneration In Rats Research Articles

Targeting RIP3 inhibits osteoarthritis development by restoring anabolic-catabolic balance in the bone-cartilage unit

BackgroundOsteoarthritis (OA) is a debilitating joint disorder characterized by progressive cartilage degeneration. During OA, subchondral bone undergoes microstructural and molecular changes that precede cartilage degradation. However, specific mechanisms underlying metabolic dysregulation of the bone-cartilage unit remain unclear. This study aims to investigate the role of receptor-interacting protein kinase-3 (RIP3) in OA progression, focusing on bone-cartilage metabolic homeostasis. MethodsRIP3-mediated pathological and metabolic alterations in chondrocytes, osteoblasts, and bone marrow-derived macrophages (BMMs) were evaluated. RIP3-mediated OA manifestations in cartilage and, more importantly, subchondral bone were determined by intra-articular overexpression of RIP3 in rats. The protective effect of RIP3 deficiency on the bone-cartilage unit during OA was systematically investigated using Rip3 knockout mice. The CMap database was used to screen for compounds that abrogate RIP3-induced OA pathological changes. ResultsRIP3 was upregulated in the cartilage and subchondral bone of OA patients and post-traumatic OA mouse model. RIP3 overexpression not only inhibited extracellular matrix (ECM) anabolism in chondrocytes but also attenuated osteoblast differentiation, whereas RIP3 deficiency blunted receptor activator of NF-kappaB ligand-mediated osteoclastogenesis of BMMs. Intra-articular RIP3 overexpression induced the imbalance of SP7+ osteoblasts/tartrate-resistant acid phosphatase (TRAP)+ osteoclasts within the subchondral bone in addition to cartilage degeneration in rats, while Rip3 deletion significantly improved structural outcomes of the bone-cartilage unit, and achieved pain relief as well as functional improvement in surgery-induced and spontaneous OA mouse models. Mechanistically, RIP3 initiates OA by perturbing critical events, including cartilage metabolism, inflammatory responses, senescence, and osteoclast differentiation. Clofibrate, a hypolipidemic drug, was identified as a novel RIP3 inhibitor that reverses ECM catabolism in OA. ConclusionsRIP3 is an essential governor of whole joint metabolic homeostasis by regulating both cartilage metabolism and subchondral bone remodeling. Reconstruction of the bone-cartilage unit by targeting RIP3 might provide a two-birds-one-stone approach for the development of future OA therapies.

Ginkgolide C slows the progression of osteoarthritis by activating Nrf2/HO-1 and blocking the NF-κB pathway.

Osteoarthritis (OA) is driven by chronic low-grade inflammation and subsequent cartilage degradation. OA is the most prevalent degenerative joint disease worldwide, and its treatment remains a challenge. The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of ginkgolide C (GC). Protective effects of GC on hydrogen peroxide (H2O2)-treated rat chondrocytes were evaluated using ELISA, qPCR, western blot analysis, flow cytometry, ROS detection and immunofluorescence in vitro. Ameliorating effects of GC on cartilage degeneration in rats were evaluated through behavioral assays, microcomputed tomography, histopathological analysis, western blot analysis and ELISA in vivo. In vitro, GC treatment inhibited the release of pro-apoptotic factors induced by H2O2 and promoted the release of the anti-apoptotic proteins. In addition, GC decreased the expression of matrix metalloproteinase (MMP3 and MMP13), thrombospondin motifs 4 (ADAMTS4), and inflammatory mediators inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and SOX9 thereby inhibiting extracellular matrix (ECM) degradation. Mechanistically, GC exerts its anti-apoptotic and anti-inflammatory effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, In a rat model with post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT), GC inhibited joint pain, cartilage destruction, and abnormal bone remodeling of subchondral bone. GC inhibited H2O2-induced chondrocyte apoptosis through Nrf2/HO-1 and NF-κB axis, exerted anti-inflammatory effects, and inhibited cartilage degeneration in rat OA. Our findings advanced the concept that GC may contribute to cartilage metabolism through anti-inflammatory and anti-apoptotic effects, and the identified GC is a potential therapeutic agent for the treatment of OA.

Effect of Dexamethasone on Cartilage Degeneration in Rats with Collagen-induced Arthritis

Effect of Dexamethasone on Cartilage Degeneration in Rats with Collagen-induced Arthritis

Mechanism of Delaying Cartilage Degeneration in Knee Osteoarthritis with Rongjin Niantong Recipe Based on lncRNA NEAT1 and Nrf2/ARE Pathway

<bold>Objective</bold> To evaluate the effect of Rongjin Niantong Recipe on knee osteoarthritis model rats, and to explore the mechanism of delaying cartilage degeneration in knee osteoarthritis based on long noncoding RNA (lncRNA) NEAT1 and Nrf2/ARE pathway. <bold>Methods</bold> After adaptive feeding for one week, a total of 45 SPF SD rats aged two months were randomly divided into blank group and sodium iodoacetate group, with 15,30 cases in each group. Under anesthesia, 0.05 mL sodium iodoacetate at a concentration of 20 mg/mL was injected into the right knee joint to establish the knee osteoarthritis model, and the blank group was injected with the same amount of normal saline. After modeling was assessed to be successful, the sodium iodoacetate group were randomly divided into model group and Rongjin Niantong Recipe group, with 15 cases in each group. The Rongjin Niantong Recipe group were given 1.9 g/(kg·d) the medicine by gavage, and the blank group and the model group were given the same amount of normal saline by gavage for eight weeks. After the intervention, all groups were sacrificed under anesthesia, and the right knee tissues were separated and collected; HE staining was used to observe the pathological changes; Western blot was used to detect the expression levels of Nrf2, heme oxygenase-1 (HO-1), NAD (P) H quinone oxidoreductase-1 (NQO-1), kelch like ECH-associated protein 1 (Keap1) and inducible nitric oxide synthase (iNOS) in cartilage; Real-time PCR was used to detect the expression of lncRNA NEAT1 in cartilage tissue. <bold>Results</bold> 1) Pathological changes of cartilage tissue: the cartilage matrix was light red and uniform, with complete tissue structure and clear tissue margins of each layer in the blank group; in the model group, the chondrocytes grew in clusters with thinner tangent layer. The surface layer was destroyed and the transitional layer and the radiation layer became disordered and partial calcified. There were obvious calcifications in the calcified layer. In addition, the adhesion line between the calcified layer and the subchondral bone fluctuated greatly and was discontinuous. The tangents of the superficial layer in the Rongjin Niantong Recipe group were completed and basically paralleled to the articular surface, and the transitional layer, radiation layer, calcification layer and other layers were relatively clear. 2) Expressions of Nrf2/ARE pathway related proteins in the cartilage: compared with the blank group, the protein expression levels of Keap1 and iNOS of the model group significantly increased (<italic>P</italic>&lt;0.05) and the protein expression levels of Nrf2, HO-1 and NQO-1 significantly decreased (<italic>P</italic>&lt;0.05). Compared with the model group, the protein expression levels of Keap1 and iNOS in the Rongjin Niantong Recipe group significantly decreased (<italic>P</italic>&lt;0.05), while the protein expression levels of Nrf2, HO-1 and NQO-1 significantly increased (<italic>P</italic>&lt;0.05). 3) Expressions of lncRNA NEAT1 in cartilage: compared with the blank group, the expression level of lncRNA NEAT1 in the model group was significantly higher (<italic>P</italic>&lt;0.05); compared with the model group, the expression level of lncRNA NEAT1 in the Rongjin Niantong Recipe group significantly decreased (<italic>P</italic>&lt;0.05). <bold>Conclusion</bold> Rongjin Niantong Recipe can delay cartilage degeneration in rats with osteoarthritis. The mechanism may be related to the down-regulation of lncRNA NEAT1 level, up-regulation of Nrf2 signal and antioxidant signal molecules expressions, and down-regulation of pro-oxidation signal molecules and inhibition of oxidative stress level.

Pulsed electromagnetic field alleviates synovitis and inhibits the NLRP3/Caspase-1/GSDMD signaling pathway in osteoarthritis rats

ABSTRACT Low-grade inflammation is a key mediator of the pathogenesis of Osteoarthritis (OA). Pulsed electromagnetic field (PEMF) can improve the symptoms of OA and potentially acts as an anti-inflammatory. The aim of this study was to investigate the effect of the PEMF on OA and its relationship with the NLRP3/Caspase-1/GSDMD signaling pathway.18 Three-month-old Sprague-Dawley (SD) rats were randomly divided into three groups (n = 6 per group): 1) OA group, 2) OA+PEMF group (OA with PEMF exposure), 3) Control group (sham operation with placebo PEMF). Rats in the OA and OA+PEMF groups were subjected to bilateral anterior cruciate ligament transection and ovariectomy. PEMF scheme: Pulse waveform, 3.82 mT, 8 Hz, 40 min/day, 5 days a week, for 12 weeks. The expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and MMP-13 were detected by qRT-PCR and Western blot. The pathological structures of OA were monitored with Safranin O/fast green staining and hematoxylin eosin staining. Our results showed that PEMF alleviated the degree of inflammation and degeneration of cartilage in rats with OA, based on the histopathological changes and decline of the expression of IL-1β and MMP-13. Moreover, the over-expression of NLRP3, Caspase-1, and GSDMD in the cartilage of the OA rats decreased after PEMF treatment. These results suggested that PEMF could be a highly promising noninvasive strategy to slow down the progression of OA and inhibition of the NLRP3/Caspase-1/GSDMD signaling pathway might be involved in the beneficial effect of PEMF.

A green-lipped mussel reduces pain behavior and chondrocyte inflammation and attenuated experimental osteoarthritis progression.

The green-lipped mussel (GLM) contains novel omega-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and joint-protecting properties. Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage; oxidative stress plays a role in the pathogenesis of OA. The objectives of this study were to investigate the in vivo effects of the GLM on pain severity and cartilage degeneration using an experimental rat OA model, and to explore the mode of action of GLM. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) into the knee. Oral GLM was initiated on the day after 3dyas of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed both macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine, and inducible nitric oxide synthase (iNOS) in knee joints. Also, the GLM was applied to OA chondrocyte, and the expression on catabolic marker and necroptosis factor were evaluated by real-time polymerase chain reaction. Administration of the GLM improved pain levels by preventing cartilage damage and inflammation. GLM significantly attenuated the expression levels of mRNAs encoding matrix metalloproteinase-3 (MMP-3), MMP-13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. GLM decreased the expression levels of the necroptosis mediators RIPK1, RIPK3, and the mixed lineage kinase domain-like protein (MLKL) in IL-1β-stimulated human OA chondrocytes. Thus, GLM reduced pain and cartilage degeneration in rats with experimentally induced OA. The chondroprotective properties of GLM included suppression of oxidative damage and inhibition of catabolic factors implicated in the pathogenesis of OA cartilage damage. We suggest that GLM may usefully treat human OA.

Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway.

With the gradual deepening of understanding of systemic health and quality of life, the factors affecting osteoarthritis (OA) are not limited to mechanical injury, metabolic abnormality, age and obesity, etc., but circadian rhythm, which plays a non-negligible role in human daily life. The purpose of this study was to explore the molecular mechanism of chronic circadian rhythm disturbance (CRD) inducing cartilage OA-like degeneration. Rats with the anterior cruciate ligament excision transection (ACLT) were used to establish the early-stage OA model (6-week). The light/dark (LD) cycle shifted 12 h per week for 22 weeks in order to establish a chronic CRD model. BMAL1 knockdown (KD) and Wnt/β-catenin pathway inhibition were performed in chondrocytes. The contents of proinflammatory factors and OA biomarkers in serum and chondrocyte secretions were detected by ELISA. Pathological and immunohistochemical staining of articular cartilage indicated the deterioration of cartilage. WB and qPCR were used to evaluate the relationship between matrix degradation and the activation of Wnt/β-catenin signaling pathway in chondrocytes. We found that chronic CRD could cause OA-like pathological changes in knee cartilage of rats, accelerating cartilage matrix degradation and synovial inflammation. The expression of MMP-3, MMP-13, ADAMTS-4, and β-catenin increased significantly; BMAL1, Aggrecan, and COL2A1 decreased significantly in either LD-shifted cartilage or BMAL1-KD chondrocytes. The expression of β-catenin and p-GSK-3β elevated, while p-β-catenin and GSK-3β diminished. The inhibitor XAV-939 was able to mitigated the increased inflammation produced by transfected siBMAL1. Our study demonstrates that chronic CRD disrupts the balance of matrix synthesis and catabolic metabolism in cartilage and chondrocytes, and it is related to the activation of the canonical Wnt/β-catenin signaling pathway.

Effects of cartilage progenitor cells and microRNA-140 on repair of osteoarthritic cartilage injury

To summarize the effect of cartilage progenitor cells (CPCs) and microRNA-140 (miR-140) on the repair of osteoarthritic cartilage injury, and analyze their clinical prospects. The recent researches regarding the CPCs, miR-140, and repair of cartilage in osteoarthritis (OA) disease were extensively reviewed and summarized. CPCs possess the characteristics of self-proliferation, expression of stem cell markers, and multi-lineage differentiation potential, and their chondrogenic ability is superior to other tissues-derived mesenchymal stem cells. CPCs are closely related to the development of OA, but the autonomic activation and chondrogenic ability of CPCs around the osteoarthritic cartilage lesion cannot meet the requirements of complete cartilage repair. miR-140 specifically express in cartilage, and has the potential to activate CPCs by inhibiting key molecules of Notch signaling pathway and enhance its chondrogenic ability, thus promoting the repair of osteoarthritic cartilage injury. Intra-articular delivery of drugs is one of the main methods of OA treatment, although intra-articular injection of miR-140 has a significant inhibitory effect on cartilage degeneration in rats, it also exhibit some limitations such as non-targeted aggregation, low bioavailability, and rapid clearance. So it is a good application prospect to construct a carrier with good safety, cartilage targeting, and high-efficiency for miR-140 based on articular cartilage characteristics. In addition, CPCs are mainly dispersed in the cartilage surface, while OA cartilage injury also begins from this layer, it is therefore essential to emphasize early intervention of OA. miR-140 has the potential to activate CPCs and promote the repair of cartilage injury in early OA, and it is of great clinical significance to further explore the role of miR-140 in OA etiology and to develop new OA treatment strategies based on miR-140.

Catabolic changes of rat temporomandibular joint discs induced by unilateral anterior crossbite.

The temporomandibular joint (TMJ) disc plays a role in joint movement and in load absorbance and distribution. An experimental unilateral anterior crossbite (UAC) prosthesis induces mandibular condylar cartilage degeneration in rats. However, the changes in the articular disc are still unknown. To describe changes in the TMJ discs of UAC rats. The discs of fifty-four Sprague-Dawley rats, equally distributed into a UAC group and an age-matched sham-operated control group at 4, 12 and 20weeks (n=9), were evaluated by gross and histomorphological observation and by detection at the mRNA or protein expression levels of the markers related to the matrix elements. No macro- or micro-morphological differences were observed between groups. However, there were catabolic degradative changes at the molecular level in the UAC group, showing a significant reduction in the mRNA and/or protein expression levels of many molecules. The reduction became worse with time (P<0.05). The reduced molecules included: (a) those related to the extracellular matrix, such as type I collagen, decorin and fibromodulin; (b) those related to chondrogenesis, such as type II collagen and aggrecan; and (c) those related to osteogenesis, such as alkaline phosphatase and runt-related transcription factor 2. The mRNA expression of vascular endothelial growth factor did not change. In contrast, fibronectin, which can promote wound healing, and its N-terminal fragment, which can induce cartilage degradation, were accumulated (P<0.05). TMJ discs were stimulated to catabolic changes by the aberrant dental occlusion and seemed to go to inanimate with time.

Effects of treadmill training and EVOO enriched diet on cartilage degeneration in rats with ACLT.

The beneficial effects of Extra Virgin Olive Oil (EVOO), the main fat source in Mediterranean diet, are widely studied thanks to its anti-inflammatory and antioxidant properties. Lubricin is a chondroprotective glycoprotein, with lubricant properties. A joint injury causes an increased cytokine expression, associated with decreased lubricin synthesis and predisposition to cartilage degeneration. The aim of this study was to evaluate the beneficial role of EVOO-enriched diet and physical activity, on osteoarthritic cartilage of rats. These effects were assessed through lubricin and interleukin-6 expression in rat joint tissues. Osteoarthritis was induced mechanically by anterior cruciate ligament transection (ACLT). Forty-eight 3-month-old male Wistar rats were used for this study. Experiments and surgical procedures for ACLT were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee (I.A.C.U.C.) of the University of Catania, European Community Council Directive and the Italian Animal Protection Law (Protocol n. 2112015-PR, Italian Ministry of Health). The 48 animals were divided into 6 groups: 1 – control rats (no ACLT, common die); 2 – rats with ACLT and common diet (experimental control); 3 – rats with ACLT, common diet and treadmill training; 4 – rats with ACLT, Sicilian EVOO and treadmill training; 5 – rats with ACLT, Tunisian EVOO and treadmill training; 6 – rats with ACLT, Tunisian EVOO and leaves extract and treadmill training. To this purpose, we performed histomorphometric, histological, immunocytochemical, immunohistochemical and biochemical analysis for lubricin and interleukin-6 evaluations in articular cartilage and synovial fluid of rats. Furthermore, skeletal muscle (anterior tibial) and liver tissue were used to perform histological analyses to exclude respectively hepatic steatosis and sarcopenia. The results showed the beneficial effect of physical activity and EVOO supplementation on the rat articular cartilage. ACLT determined an increase in interleukin-6 expression and a significant decrease in the lubricin expression, while physical activity and EVOO supplemented diet, determined that the values returned to a normal level when compared to the control group. Moreover, EVOO does not cause hepatic steatosis and muscle fibers of all groups did not show damaged histological structure. Our findings suggest that mechanical stimulation is able to increase the release of lubricin in articular cartilage, while the anti-inflammatory properties of EVOO reduces the expression of interleukin-6. In conclusion, the results showed a beneficial effect of the conjunction of EVOO-based diet, corresponding to the Mediterranean diet, and physical activity on the preservation of articular cartilage tissue. Support or Funding Information This study was supported by the University Research Project Grant (Triennial Research Plan 2016–2018), University of Catania, Italy. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Vitexin alleviates ER-stress-activated apoptosis and the related inflammation in chondrocytes and inhibits the degeneration of cartilage in rats.

Excessive extracellular matrix degradation and chondrocyte apoptosis are the pathological features of osteoarthritis (OA). The ability of flavonoid compounds isolated from Chinese hawthorn leaves to exert protective effects on several diseases, via inhibition of oxidative stress and inflammation, has been demonstrated in several studies. This study explored the effects of vitexin on chondrocytes, and the underlying mechanisms thereof. Vitexin, an active ingredient in hawthorn leaf extracts, was shown to exert protective effects on chondrocytes, by inhibiting the expression of GRP78 and PDI, and an apoptotic protein (CHOP) induced by interleukin-1β. It also modulated thapsigargin-induced upregulation of GRP78 and PDI and subsequently an apoptotic protein (CHOP). Among rat chondrocytes, both the ER stress-activated nuclear factor kappa B (NF-κB) pathway and the induced expression of inflammatory cytokines (IL-6 and TNF-α) were significantly inhibited by vitexin. Finally, vitexin attenuated the progression of OA in vivo in rats. Taken together, all data demonstrate the relationship of ER stress and inflammation in the progression of OA, the ability of vitexin to protect chondrocytes and thus its therapeutic potential in patients with OA.

Chondroprotective effects of alpha-lipoic acid in a rat model of osteoarthritis

ABSTRACTObjective: The purpose of this study was to investigate whether alpha-lipoic acid (ALA) confers a chondroprotective effect on articular cartilage in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA).Methods: Fifty male SD rats were divided into five groups, including SHAM-operated, MIA-induced OA, and three experimental groups treated with 50-, 100-, or 200-mg/kg ALA. After 14 d of ALA treatment, rats were sacrificed for joint macroscopic and histology assessments. The gene and protein expressions of markers related to chondrocyte phenotype, caspase proteins, NADPH oxidase 4 (Nox4), p22phox, activation of nuclear factor-κB (NF-κB), and endoplasmic reticulum (ER) stress were measured by Western blot analyses or qRT-PCR.Results: The results showed that MIA injection successfully induced OA by causing cartilage degeneration. Morphological and histological examinations demonstrated that ALA treatment, especially 200 mg/kg of ALA, significantly ameliorated cartilage degeneration in rats with MIA-induced OA. ALA could effectively increase the levels of the collagen type II and aggrecan genes and inhibit apoptosis-related proteins expression. ALA reduced biomakers of oxidative damage and over-expression levels of Nox4 and p22phox. ALA also suppressed ER stress and inhibited the activation of NF-κB pathway. Moreover, ALA obviously inhibited TNF-α secretion and Wnt/β-catenin signaling way.Conclusion: These findings indicated that ALA might be a potential therapeutic agent for the protection of articular cartilage against progression of OA through inhibition of oxidative stress, ER stress, inflammatory cytokine secretion, and Wnt/β-catenin activation.

Spatial and temporal changes of subchondral bone proceed to articular cartilage degeneration in rats subjected to knee immobilization

This study was aimed to investigate the spatial and temporal changes of subchondral bone and its overlying articular cartilage in rats following knee immobilization. A total of 36 male Wistar rats (11-13 months old) were assigned randomly and evenly into 3 groups. For each group, knee joints in 6 rats were immobilized unilaterally for 1, 4, or 8 weeks, respectively, while the remaining rats were allowed free activity and served as external control groups. For each animal, femurs at both sides were dissected after sacrificed. The distal part of femur was examined by micro-CT. Subsequently, femoral condyles were collected for further histological observation and analysis. For articular cartilage, significant changes were observed only at 4 and 8 weeks of immobilization. The thickness of articular cartilage and chondrocytes numbers decreased with time. However, significant changes in subchondral bone were defined by micro-CT following immobilization in a time-dependent manner. Immobilization led to a thinner and more porous subchondral bone plate, as well as a reduction in trabecular thickness and separation with a more rod-like architecture. Changes in subchondral bone occurred earlier than in articular cartilage. More importantly, immobilization-induced changes in subchondral bone may contribute, at least partially, to changes in its overlying articular cartilage.

Synovial mesenchymal stem cells promote meniscus regeneration augmented by an autologous Achilles tendon graft in a rat partial meniscus defect model.

Although meniscus defects and degeneration are strongly correlated with the later development of osteoarthritis, the promise of regenerative medicine strategies is to prevent and/or delay the disease's progression. Meniscal reconstruction has been shown in animal models with tendon grafting and transplantation of mesenchymal stem cells (MSCs); however, these procedures have not shown the same efficacy in clinical studies. Here, our aim was to investigate the ability of tendon grafts pretreated with exogenous synovial-derived MSCs to prevent cartilage degeneration in a rat partial meniscus defect model. We removed the anterior half of the medial meniscus and grafted autologous Achilles tendons with or without a 10-minute pretreatment of the tendon with synovial MSCs. The meniscus and surrounding cartilage were evaluated at 2, 4, and 8 weeks (n = 5). Tendon grafts increased meniscus size irrespective of synovial MSCs. Histological scores for regenerated menisci were better in the tendon + MSC group than in the other two groups at 4 and 8 weeks. Both macroscopic and histological scores for articular cartilage were significantly better in the tendon + MSC group at 8 weeks. Implanted synovial MSCs survived around the grafted tendon and native meniscus integration site by cell tracking assays with luciferase+, LacZ+, DiI+, and/or GFP+ synovial MSCs and/or GFP+ tendons. Flow cytometric analysis showed that transplanted synovial MSCs retained their MSC properties at 7 days and host synovial tissue also contained cells with MSC characteristics. Synovial MSCs promoted meniscus regeneration augmented by autologous Achilles tendon grafts and prevented cartilage degeneration in rats. Stem Cells 2015;33:1927–1938

Preventive and therapeutic effects of Yiqi Huayu Recipe on degeneration of articular cartilage in rats with osteoarthritis

To study the efficacy and possible mechanism of Yiqi Huayu Recipe (YQHYR), a compound traditional Chinese herbal medicine, in preventing and treating degeneration of the articular cartilage in rats with osteoarthritis (OA). A total of 90 one-month-old SD rats were randomly divided into normal control group, untreated group and YQHYR group, with 30 rats in each group. The osteoarthritis was induced by shoulder disarticulation plus upright posture in rats. The rats in YQHYR group were treated with YQHYR at 5-, 7- and 9-month old (4, 6 and 8 months after the surgery) for one month. Ten rats in each subgroup were sacrificed at 6-, 8- and 10-month old (5, 7 and 9 months after the surgery) respectively and the knee joint samples were harvested for detection. Safranin-O/fast green staining was performed to examine the morphology of articular cartilage. The expressions of type II collagen (Col2A1), aggrecan-1 (Agc1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs were evaluated by real-time fluorescent quantitation polymerase chain reaction. Histological analysis showed that the structure of articular cartilage was seriously destroyed in rats in the untreated group. On the contrary, the degenerative changes of the articular cartilage in the YQHYR group were dropped off. Real-time fluorescent quantitation polymerase chain reaction showed that expressions of Agc1, TIMP-1 and Col2A1 mRNAs were up-regulated in 6- and 10-month-old rats in the YQHYR group as compared with those in the untreated group (P<0.01, P<0.05), but there was no significant difference in expression of MMP-13 mRNA between the YQHYR group and the untreated group. The expression of Agc1 mRNA was up-regulated and the expression of MMP-13 mRNA was down-regulated in the 8-month-old rats in YQHYR group as compared with those in the untreated group (P<0.01). YQHYR can promote the synthesizing of aggrecan and type II collagen in chondrocytes and delay articular cartilage degradation in OA rats.