• Journal of the Korean Applied Science and Technology
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• v.38 no.2
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• pp.368-377
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• 2021

The present study aimed to evaluate the effects of radiation mutant Perilla frutescens var. crispa and Atractylodes macrocephala Koidzumi complex extract(Perilla frutescens var. crispa complex extract) on the mediators related to degenerative arthritis in a monosodium iodoacetate-induced rat model of degenerative arthritis. Perilla frutescens var. crispa complex extract was administered orally at doses of 25, 50 or 100 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 µl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral Perilla frutescens var. crispa complex extract for another 4 weeks. It was evaluated that the treatment effects based on serum bio-markers, and morphological and histopathological analysis of the knee joints. Compared with those in negative control rats, the Perilla frutescens var. crispa complex extract treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., TNF-α, MMP-3, COX-2, PGE₂, COMP, and Aggrecan). Otherwise, it was significantly increased the production of CTX-2 in cartilage absorption mediators. In addition, the Perilla frutescens var. crispa complex extract treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that the Perilla frutescens var. crispa complex extract improved degenerative arthritis symptoms. Thus, the Perilla frutescens var. crispa complex can be used in food material for the management of degenerative arthritis.

• Journal of Nutrition and Health
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• v.56 no.3
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• pp.231-246
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• 2023

Purpose: The aim of this study was to investigate the anti-osteoarthritic effect of the ethanol extract of Boswellia serrata gum resin (FJH-UBS) enriched with keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid compared to the conventional Boswellia serrata extract by adding the process of removing oil with hexane, in the monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods: Sprague-Dawley (SD) rats were orally administered 0, 40, or 80 mg of FJH-UBS/kg body weight (BW)/day for 5 weeks and injected with MIA intra-articularly into right knee joints on day 15 to induce osteoarthritis. Changes in the knee joint microarchitecture, cartilage degradation, the expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) in serum and synovia were observed. Results: Oral administration of FJH-UBS (80 mg/kg BW/day) reduced MIA-induced knee swelling and cartilage degradation and increased the expression of type II collagen and aggrecan in articular cartilage. Furthermore, FJH-UBS administration reduced MIA-induced increases in the serum levels of prostaglandin E2, leukotriene B4, interleukin (IL)-1β, IL-6, and MMP-13, and MIA-induced increases in the mRNA expressions of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, and MMP-13 in the synovia of knee joints. Conclusion: These results indicate that FJH-UBS exerts its anti-osteoarthritic effects by suppressing the expressions of inflammatory cytokines and MMPs and, thus, cartilage degradation. Furthermore, they suggest that FJH-UBS has potential use as a functional food that improves joint and cartilage health.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.2907-2909
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• 2012

A disintegrin and metalloprotease with thrombospondin domains (ADAMTS) are a member of peptidase and involved in processing of von Willebrand factor as well as cleavage of aggrecan, versican, brevican and neurocan. Among 19 subfamilies of human ADAMTS, ADAMTS-4 is a zinc-binding metalloprotease and is a famous therapeutic target for arthritis. It has been reported that a flavonoid luteolin shows inhibitory activity against ADMATS-4. In this study, we verified that luteolin is a potent inhibitor of ADAMTS-4 and probed the molecular basis of its action. On the basis of a docking study, we proposed a binding model between luteolin and ADAMTS-4 in which 3',4'-dihydroxyl groups in luteolin formed hydrogen bonding with ADMATS-4 and these interactions are important for its inhibitory activity against ADAMTS-4.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.53-62
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• 2016

Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride ($CoCl_2$) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of $CoCl_2$ preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. $CoCl_2$ treatment of MSCs markedly increased HIF-$1{\alpha}$ and VEGF mRNA, and protein expression of HIF-$1{\alpha}$. Temporary preconditioning of MSCs with $CoCl_2$ induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. $CoCl_2$ also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. $CoCl_2$ suppressed the expression of adipogenic markers including $PPAR{\gamma}$, aP2, and $C/EBP{\alpha}$, and inhibited adipogenesis. Temporary preconditioning with $CoCl_2$ could affect the multi-lineage differentiation of MSCs.

• Journal of Korean Neurosurgical Society
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• v.53 no.6
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• pp.323-330
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• 2013

Objective : To develop a simple, reproducible model of disc degeneration in rabbits through percutaneous annular puncture and to confirm the degree of degeneration over time. Methods : Fifteen New Zealand white rabbits (4 to 5 months old and weighing approximately 3 to 3.5 kg each) underwent annular puncture of the L2-L3, L3-L4, and L4-L5 discs. Rabbits were sacrificed at 4, 8, or 20 weeks after puncture. For a longitudinal study to assess changes in disc height over time, serial X-rays were performed at 0, 2, 4, 8, and 20 weeks for rabbits in the 20-week group. Upon sacrifice, the whole spinal column and discs were extracted and analyzed with magnetic resonance imaging (MRI), real time reverse transcriptase-polymerase chain reaction, and histological staining. Results : The X-rays showed a slow, progressive decrease in disc height over time. Significant disc space narrowing compared to preoperative disc height was observed during the time period (p<0.001). The MRI grade, aggrecan, and matrix metalloprotease-13 mRNA expression and hematoxylin and eosin/safranin O/anti-collagen II staining were consistently indicative of degeneration, supporting the results of the X-ray data. Conclusion : Percutaneous annular puncture resulted in slow, reproducible disc degeneration that was confirmed by radiology, biochemistry, and histology. This in vivo model can be used to study and evaluate the safety and efficacy of biologic treatments for degenerative disc disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.2
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• pp.79-87
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• 2022

In this study, extracts of Boswellia serrata gum resin, Curcuma longa rhizome, and Terminalia chebula fruit were combined in different ratios, and their anti-osteoarthritis effects were compared to determine which combination had the best synergistic effect. B. serrata, C. longa, and T. chebula extracts in a 2:1:2 ratio exhibited higher antioxidative activity in scavenging DPPH radicals than did the individual extracts alone or the other extract combinations. Additionally, the 2:1:2 combination significantly improved the levels of enzymatic antioxidants and antioxidant-related proteins. Moreover, this same combination ratio decreased the protein levels of matrix metalloproteinase (MMP) 3 and MMP13 in interleukin-1β-stimulated human articular chondrocytes (HCHs) and increased those of aggrecan and collagen type II alpha 1 chain (COL2A1). Analysis of the underlying mechanisms revealed that the 2:1:2 combination significantly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65, extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK). Therefore, the 2:1:2 combination of these three plant extracts has the best potential for use as an effective dietary supplement for improving joint health compared with the individual extracts and their other combination ratios.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.34 no.2
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• pp.91-99
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• 2012

Purpose: The purpose of this study was to evaluate the expression of osteogenic genes associated with bone regeneration on anodizing titanium surface. Methods: $20{\times}20{\times}1$ (mm) commercially pure titanium plate was made, one group was pure titanium, second group was punched, and last group was punched and anodized by electrochemical method. Through the osteogenic cell culture model, the expression of extracellular matrix proteins, such as bone morphogenetic protein-2, bone sialoprotein, aggrecan, osteocalcin, Alkaline phosphatase, collagen I had been evaluated by Real-time polymerase chain reaction, and the morphology of growing cells was evaluated by scanning electron microscopy. Results: The attachment of mesenchymal stem cell was even and well-oriented on all Ti surfaces. The osteogene expression was increased on punching groups but, decreased on anodizing surfaces in 3 week samples. Conclusion: Punched anodizing Ti has possibility be using as a dental implant material, but further in vivo study would be needed.

• Journal of Embryo Transfer
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• v.32 no.3
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• pp.193-200
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• 2017

The purpose of this study is to confirm whether spontaneous adipocyte generation during chondrogenic induction culture affects the chondrogenic differentiation of porcine skin-derived stem cells (pSSCs). For this purpose, chondrogenic differentiation characteristics and specific marker gene expression were analyzed using cell lines showing different characteristics of spontaneous adipocyte formation. Of the four different lines of pSSCs, the pSSCs-IV line showed higher Oil red O (ORO) and glycosaminoglycan (GAG) extraction levels. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that the levels of adipogenic markers peroxisome proliferator-activated receptor gamma 2 ($PPAR{\gamma}2$) and adipocyte Protein 2 (aP2) mRNAs were significantly higher in pSSCs-IV than those of the other pSSC lines (P<0.05). Among three chondrogenic markers, collagen type II (Col II) and sex determining region Y-box (Sox9) mRNAs were strongly expressed in pSSCs-IV (P<0.05), but not in aggrecan (Agg), which was significantly higher in pSSCs-II (P<0.05). These results demonstrate that the spontaneous adipocyte generation during chondrogenic differentiation has a positive effect on the chondrogenesis of pSSCs. More research is needed on the correlation between adipocyte generation and cartilage formation.

• BMB Reports
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• v.54 no.10
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• pp.528-533
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• 2021

Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1β), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OA-like condition of chondrocytes in vitro. Avn-C restrained IL-1β-mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1β, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1β treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis.

• Journal of Genetic Medicine
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• v.15 no.2
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• pp.102-106
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• 2018

Aggrecan is a proteoglycan in the extracellular matrix of growth plate and cartilaginous tissues. Aggrecanopathy has been reported as a genetic cause not only for severe skeletal dysplasia but also for autosomal dominant short stature with normal to advanced bone age. We report a novel heterozygous mutation of ACAN in a Korean family with proportionate short stature identified through targeted exome sequencing. We present a girl of 4 years and 9 months with a family history of short stature over three generations. The paternal grandmother is 143 cm tall (-3.8 as a Korean standard deviation score [SDS]), the father 155 cm (-3.4 SDS), and the index case 96.2 cm (-2.9 SDS). Evaluation for short stature showed normal growth hormone (GH) peaks in the GH provocation test and a mild delayed bone age for chronological age. This subject had clinical characteristics including a triangular face, flat nasal bridge, prognathia, blue sclerae, and brittle teeth. The targeted exome sequencing was applied to detect autosomal dominant growth palate disorder. The novel variant c.910G>A (p.Asp304Asn) in ACAN was identified and this variant was found in the subject's father using Sanger sequencing. This is the first case of Korean familial short stature due to ACAN mutation. ACAN should be considered for proportionate idiopathic short stature, especially in cases of familial short stature.