Jeong-Im Woo
University of California, Los Angeles, Dept. of Head and Neck Surgery, Department Member
- A Cell Biologist moved to the Cell therapy company three years ago after 20 plus years of Academia.edit
Inflammatory response is commonly involved in the pathogenesis of various cochlear diseases such as acoustic trauma and cisplatin ototoxicity. Previously, we have demonstrated that the spiral ligament fibrocytes play a pivotal role in... more
Inflammatory response is commonly involved in the pathogenesis of various cochlear diseases such as acoustic trauma and cisplatin ototoxicity. Previously, we have demonstrated that the spiral ligament fibrocytes play a pivotal role in cochlear inflammation through secretion of chemokines such as CCL2 and CXCL2 in response to pro-inflammatory signals. In this study, we aim to determine molecular mechanism involved in negative modulation of cochlear inflammation. We found that IL-10 inhibits SLF’s CCL2 up-regulation and migration of THP-1 cells in response to SLF-derived molecules. The SLFs appeared to up-regulate HMOX1 expression via NRF-2 activation. The inhibitory effect of IL-10 was mimicked by CoPP and CORM-3 but was blocked by silencing of IL-10RA and HMOX1. IL-10 was found to inhibit binding of p65 NFκB to the enhancer region of the CCL2 gene. IL-10 deficiency appeared to enhance cochlear inflammation secondary to nontypeable H. influenzae-induced otitis media. Furthermore, we ...
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J. Biochem. Mol. ВЫ. Vol. 30, No. 1, pp. 37-40 January 31. 1997 Deoxyribonucleic Acid Was Responsible for the Anticoagulatory Effect of an Earthworm, Lumbricus rubellus Seung R. Paik, Jeong-Im Woo, Gyoung-Mi Kim, Jin-Mo Cho, Kyoung-Hee Yu... more
J. Biochem. Mol. ВЫ. Vol. 30, No. 1, pp. 37-40 January 31. 1997 Deoxyribonucleic Acid Was Responsible for the Anticoagulatory Effect of an Earthworm, Lumbricus rubellus Seung R. Paik, Jeong-Im Woo, Gyoung-Mi Kim, Jin-Mo Cho, Kyoung-Hee Yu and Chung-Soon ...
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Primary open angle glaucoma (POAG) features an optic neuropathy, elevated aqueous humor (AH) TGFβ2, and major risk factors of central corneal thickness (CCT), increasing age and intraocular pressure (IOP). We examined Tight skin (Tsk)... more
Primary open angle glaucoma (POAG) features an optic neuropathy, elevated aqueous humor (AH) TGFβ2, and major risk factors of central corneal thickness (CCT), increasing age and intraocular pressure (IOP). We examined Tight skin (Tsk) mice to see if mutation of fibrillin-1, a repository for latent TGFβ, is associated with characteristics of human POAG. We measured: CCT by ocular coherence tomography (OCT); IOP; retinal ganglion cell (RGC) and optic nerve axon counts by microscopic techniques; visual electrophysiologic scotopic threshold responses (STR) and pattern electroretinogram (PERG); and AH TGFβ2 levels and activity by ELISA and MINK epithelial cell-based assays respectively. Tsk mice had open anterior chamber angles and compared with age-matched wild type (WT) mice: 23% thinner CCT (p < 0.003); IOP that was higher (p < 0.0001), more asymmetric (p = 0.047), rose with age (p = 0.04) and had a POAG-like frequency distribution. Tsk mice also had RGCs that were fewer (p <...
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Niemann-Pick type C2 (NPC2) protein has been characterized as a cholesterol-binding protein. Its loss leads to NPC2 disease, an inherited neurodegenerative disorder. When analyzing gene expression profile, we noticed high expression of... more
Niemann-Pick type C2 (NPC2) protein has been characterized as a cholesterol-binding protein. Its loss leads to NPC2 disease, an inherited neurodegenerative disorder. When analyzing gene expression profile, we noticed high expression of both NPC2 and its receptor, mannose 6-phosphate receptor (MPR), in murine hematopoietic stem cells. NPC2 protein, in the presence of thrombopoietin (TPO), causes an increase in CFU-GEMM (colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte) and a decrease in CFU-GM (colony-forming unit-granulocyte-macrophage) colony number in colony-forming cell (CFC) assays. This effect is independent of cholesterol binding but does require the presence of MPR. With M07e cells, a TPO-dependent hematopoietic leukemia cell line, NPC2 can inhibit TPO-induced differentiation and enhance TPO-mediated anti-apoptosis effects. Strikingly, these results are not observed under the standard 20% O2 level of the standard incubator, but rather at 7% O2, the physiolog...
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Research Interests: Engineering, Materials Science, Tissue Engineering, Ultrasound, Medicine, and 12 moreGene expression, Biomedical, Biological Sciences, Humans, Ultrasonics, Alginates, Articular Cartilage Wear, Chondrocytes, Microspheres, Gene Expression Regulation, Extracellular Matrix Proteins, and D-glucuronic acid
Inner ear dysfunction secondary to chronic otitis media (OM), including high-frequency sensorineural hearing loss or vertigo, is not uncommon. Although chronic middle ear inflammation is believed to cause inner ear dysfunction by entry of... more
Inner ear dysfunction secondary to chronic otitis media (OM), including high-frequency sensorineural hearing loss or vertigo, is not uncommon. Although chronic middle ear inflammation is believed to cause inner ear dysfunction by entry of OM pathogen components or cytokines from the middle ear into the inner ear, the underlying mechanisms are not well understood. Previously, we demonstrated that the spiral ligament fibrocyte (SLF) cell line up-regulates monocyte chemotactic protein 1 (MCP-1) expression after treatment with nontypeable Haemophilus influenzae (NTHI), one of the most common OM pathogens. We hypothesized that the SLF-derived MCP-1 plays a role in inner ear inflammation secondary to OM that is responsible for hearing loss and dizziness. The purpose of this study was to investigate the signaling pathway involved in NTHI-induced MCP-1 up-regulation in SLFs. Here we show for the first time that NTHI induces MCP-1 up-regulation in the SLFs via Toll-like receptor 2 (TLR2)-dep...
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Background Lysozyme is an antimicrobial innate immune molecule degrading peptidoglycan of the bacterial cell wall. Lysozyme shows the ubiquitous expression in wide varieties of species and tissues including the tubotympanum of mammals. We... more
Background Lysozyme is an antimicrobial innate immune molecule degrading peptidoglycan of the bacterial cell wall. Lysozyme shows the ubiquitous expression in wide varieties of species and tissues including the tubotympanum of mammals. We aim to investigate the effects of lysozyme depletion on pneumococcal clearance from the middle ear cavity. Methods Immunohistochemistry was performed to localize lysozyme in the Eustachian tube. Lysozyme expression was compared between the wild type and the lysozyme M-/- mice using real time quantitative RT-PCR and western blotting. Muramidase activity and bactericidal activity of lysozyme was measured using a lysoplate radial diffusion assay and a liquid broth assay, respectively. To determine if depletion of lysozyme M increases a susceptibility to pneumococal otitis media, 50 CFU of S. pneumoniae 6B were transtympanically inoculated to the middle ear and viable bacteria were counted at day 3 and 7 with clinical grading of middle ear inflammation...
Research Interests: Microbiology, RNA, Medical Microbiology, Biology, Immunohistochemistry, and 15 moreInnate immunity, Medicine, Disease susceptibility, Mice, Animals, Antimicrobial activity, Clinical Sciences, Otitis Media, Microbial Sensitivity Tests, Cell Wall, Eustachian Tube, Bactericidal Activity, Gene Expression Regulation, Gene expression profiling, and reverse transcriptase polymerase chain reaction
Background All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against... more
Background All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human β-defensin 2 is the most potent molecule and is inducible by exposure to inflammatory stimuli such as bacterial components or proinflammatory cytokines. Even though the β-defensin 2 is an important AIIM, the induction mechanism of this molecule has not been clearly established. We believe that this report is the first attempt to elucidate NTHi induced β-defensin expression in airway mucosa, which includes the middle ear. Methods Monoclonal antibody blocking method was employed in monitoring the TLR-dependent NTHi response. Two gene knock down methods – dominant negative (DN) plasmid and small interfering RNA (siRNA) – were employed to detect and confirm the involvement of several key genes in th...
Research Interests: Microbiology, Medical Microbiology, Biology, Innate immunity, Medicine, and 15 moreSignal Transduction, Cell line, Humans, Mice, Animals, Male, Clinical Sciences, Epithelial cells, Otitis Media, Beta Defensins, Monoclonal Antibody, Haemophilus influenzae, Signaling pathway, innate immune response, and Block Method
Background Otitis media (OM), one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs) recognize... more
Background Otitis media (OM), one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs) recognize OM pathogens and up-regulate chemokines. Here, we aim to determine a key molecule derived from SLFs, contributing to OM-induced inner ear inflammation. Methods Live NTHI was injected into the murine middle ear through the tympanic membrane, and histological analysis was performed after harvesting the temporal bones. Migration assays were conducted using the conditioned medium of NTHI-exposed SLFs with and without inhibition of MCP-1/CCL2 and CCR2. qRT-PCR analysis was performed to demonstrate a compensatory up-regulation of alternative genes induced by the targeting of MCP-1/CCL2 or CCR2. Results Transtympanic inoculation of live NTHI developed serous and purulent labyrinthitis after clearance of OM. THP-1 cells actively migrated and invaded the ext...
Research Interests: Microbiology, Medical Microbiology, Biology, Medicine, Extracellular Matrix, and 15 moreCell line, Humans, Infectious Disease, Mice, Animals, Male, Inner Ear, Clinical Sciences, Monocytes, Otitis Media, Labyrinthitis, Gene Expression Regulation, Haemophilus influenzae, fibroblasts, and Conditioned medium
Research Interests: Biology, Medicine, Humans, NF-kappa B, Phosphorylation, and 11 moreEpithelial cells, Adult, Beta Defensins, Base Sequence, Protein Binding, Biochemistry and cell biology, Gene Expression Regulation, Haemophilus influenzae, Molecular Sequence Data, binding sites, and Medical biochemistry and metabolomics
Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear... more
Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear epithelial cells up-regulate β-defensin 2, a model innate immune molecule, in response to nontypeable Haemophilus influenzae (NTHi), the most common OM pathogen, via TLR2 signaling. NTHi does internalize into the epithelial cells, but its intracellular trafficking and host responses to the internalized NTHi are poorly understood. Here we aimed to determine a role of cytoplasmic pathogen recognition receptors in NTHi-induced β-defensin 2 regulation and NTHi clearance from the middle ear. Notably, we observed that the internalized NTHi is able to exist freely in the cytoplasm of the human epithelial cells after rupturing the surrounding membrane. The human middle ear epithelial cells inhibited NTHi-induced β-defensin 2 production by NOD2 silencing but augme...
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Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear... more
Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear epithelial cells up-regulate b-defensin 2, a model innate immune molecule, in response to nontypeable Haemophilus influenzae (NTHi), the most common OM pathogen, via TLR2 signaling. NTHi does internalize into the epithelial cells, but its intracellular trafficking and host responses to the internalized NTHi are poorly understood. Here we aimed to determine a role of cytoplasmic pathogen recognition receptors in NTHi-induced b-defensin 2 regulation and NTHi clearance from the middle ear. Notably, we observed that the internalized NTHi is able to exist freely in the cytoplasm of the human epithelial cells after rupturing the surrounding membrane. The human middle ear epithelial cells inhibited NTHi-induced b-defensin 2 production by NOD2 silencing but augme...
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Haa-Yung Lee (hlee@hei.org) Tamotsu Takeshita (ttake@hama-med.ac.jp) Jun Shimada (Jasmd513@aol.com) Arsen Akopyan (aakopyan@hei.org) Jeong-Im Woo (jwoo@hei.org) Huiqi Pan (hpan@hei.org) Sung K Moon (smoon@hei.org) Ali Andalibi... more
Haa-Yung Lee (hlee@hei.org) Tamotsu Takeshita (ttake@hama-med.ac.jp) Jun Shimada (Jasmd513@aol.com) Arsen Akopyan (aakopyan@hei.org) Jeong-Im Woo (jwoo@hei.org) Huiqi Pan (hpan@hei.org) Sung K Moon (smoon@hei.org) Ali Andalibi (aandalibi@hei.org) Rae-Kil Park (rkpark@wonkwang.ac.kr) Sung-Ho Kang (kkdin@kku.ac.kr) Shin-Seok Kang (skang@hei.org) Jian-Dong Li (Jian-Dong_Li@urmc.rochester.edu) Robert Gellibolian (rgellibolian@hei.org) David J Lim (dlim@hei.org)
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We have previously shown that a DNA fragment is responsible for the anticoagulatory effect of an earthworm, Lumbricus rubellus. The anticoagluant increased the activated partial thromboplastin time (APTT) and also inhibited the thrombin... more
We have previously shown that a DNA fragment is responsible for the anticoagulatory effect of an earthworm, Lumbricus rubellus. The anticoagluant increased the activated partial thromboplastin time (APTT) and also inhibited the thrombin activity observed with either N--p-tosyl-L-arginine methyl ester (TAME) or H-D-phenyl-alanyl-L-pipecoil-L-arginine-p-nitroanilide (S-2238). Since trypsin digestion of the anticoagulant further increased the APTT, the possible presence of a regulatory protein for the anticoagulatory DNA was investigated by digesting the anticoagulant with trypsin and isolating the DNA fragment with C4-reversed phase HPLC. The DNA fragment lacking a regulatory protein was eluted in the flow-through fraction, and analyzed with thrombin and activated factor X. Activated factor X activity was more strongly inhibited than thrombin activity. For DNA digestion, we treated the anticoagulant with DNase and purified the DNA-binding protein with a FPLC Resource-S cation exchange...
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We have isolated a water-extracted novel regulator for blood coagulation from an earthworm, Lumbricus rubellus. As a folk remedy, the earthworm has been known to facilitate blood circulation. After complete heat inactivation of endogenous... more
We have isolated a water-extracted novel regulator for blood coagulation from an earthworm, Lumbricus rubellus. As a folk remedy, the earthworm has been known to facilitate blood circulation. After complete heat inactivation of endogenous proteases in the earthworm, an anticoagulant(s) was purified through ammonium sulfate fractionation and three consecutive gel permeation chromatography of Sephacryl S-300, Sephadex G-75, and G-150 by measuring activated partial thromboplastin time (APTT) The anticoagulant was further purified to 2,800 fold with a C4 reversed-phase HPLC This activity was stable under heat ( for 30 min) and acidic conditions (0.4 N HCl). The effects of this partially purified anticoagulant on thrombin were observed with various substrates such as N-benzoyl-DL-arginine-p-nitroanilide (BApNA), H-D-phenylalanyl-L-pipecoyl-L-arginine-p-nitroanilide (S-2238), N-p-tosyl-L-arginine methyl ester (TAME), and fibrinogen as a natural substrate. Only TAME hydrolysis, due to an e...
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Objectives: Inflammation is crucial for the pathogenesis of acquired sensorineural hearing loss, but the precise mechanism involved remains elusive. Among a number of inflammatory mediators, tumor necrosis factor-alpha (TNF-α) plays a... more
Objectives: Inflammation is crucial for the pathogenesis of acquired sensorineural hearing loss, but the precise mechanism involved remains elusive. Among a number of inflammatory mediators, tumor necrosis factor-alpha (TNF-α) plays a pivotal role in cisplatin ototoxicity. However, TNF-α alone is cytotoxic to cochlear sensory cells only at the extremely high concentrations, suggesting the involvement of other factors that may sensitize cells to TNF-α cytotoxicity. Since interferon gamma (IFN-γ) importantly contributes to the cochlear inflammatory processes, we aim to determine whether and how IFN-γ affects TNF-α cytotoxicity to cochlear sensory cells. Methods: TNF-α expression was determined with western blotting in RSL cells and immunolabeling of mouse temporal bone sections. HEI-OC1 cell viability was determined with MTT assays, cytotoxicity assays, and cytometric analysis with methylene blue staining. Cochlear sensory cell injury was determined in the organotypic culture of the m...
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Cochlear inflammatory diseases, such as tympanogenic labyrinthitis, are associated with acquired sensorineural hearing loss. Although otitis media is extremely frequent in children, tympanogenic labyrinthitis is not commonly observed,... more
Cochlear inflammatory diseases, such as tympanogenic labyrinthitis, are associated with acquired sensorineural hearing loss. Although otitis media is extremely frequent in children, tympanogenic labyrinthitis is not commonly observed, which suggests the existence of a potent anti-inflammatory mechanism modulating cochlear inflammation. In this study, we aimed to determine the molecular mechanism involved in cochlear protection from inflammation-mediated tissue damage, focusing on IL-10 and hemoxygenase-1 (HMOX1) signaling. We demonstrated that IL-10Rs are expressed in the cochlear lateral wall of mice and rats, particularly in the spiral ligament fibrocytes (SLFs). The rat SLF cell line was found to inhibit nontypeable Haemophilus influenzae (NTHi)-induced upregulation of monocyte chemotactic protein-1 (MCP-1; CCL2) in response to IL-10. This inhibition was suppressed by silencing IL-10R1 and was mimicked by cobalt Protoporphyrin IX and CO-releasing molecule-2. In addition, IL-10 ap...
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Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear... more
Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear epithelial cells up-regulate β-defensin 2, a model innate immune molecule, in response to nontypeable Haemophilus influenzae (NTHi), the most common OM pathogen, via TLR2 signaling. NTHi does internalize into the epithelial cells, but its intracellular trafficking and host responses to the internalized NTHi are poorly understood. Here we aimed to determine a role of cytoplasmic pathogen recognition receptors in NTHi-induced β-defensin 2 regulation and NTHi clearance from the middle ear. Notably, we observed that the internalized NTHi is able to exist freely in the cytoplasm of the human epithelial cells after rupturing the surrounding membrane. The human middle ear epithelial cells inhibited NTHi-induced β-defensin 2 production by NOD2 silencing but augme...
Research Interests: Inflammation, Transmission Electron Microscopy, Innate immunity, Multidisciplinary, Gene Silencing, and 14 moreSignal Transduction, Toll like receptor signaling, Cell line, Humans, Mice, Endocytosis, Animals, Male, PLoS one, Otitis Media, Beta Defensins, Cytoplasm, Haemophilus Infections Market, and Gene Expression Regulation
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Research Interests: Microbiology, RNA, Medical Microbiology, Immunohistochemistry, Innate immunity, and 14 moreStreptococcus pneumoniae, Disease susceptibility, Mice, Animals, Antimicrobial activity, Clinical Sciences, Western blot, Otitis Media, Microbial Sensitivity Tests, Cell Wall, Eustachian Tube, Bactericidal Activity, Gene Expression Regulation, and Gene expression profiling
Research Interests: Microbiology, Statistical Analysis, Medical Microbiology, Innate immunity, Signal Transduction, and 13 moreToll like receptor signaling, Cell line, Humans, Mice, Animals, Male, Signal Transduction Pathway Models, Clinical Sciences, Epithelial cells, Otitis Media, Beta Defensins, Monoclonal Antibody, and Haemophilus influenzae
Niemann-Pick type C2 (NPC2) protein has been characterized as a cholesterol-binding protein. Its loss leads to NPC2 disease, an inherited neurodegenerative disorder. When analyzing gene expression profile, we noticed high expression of... more
Niemann-Pick type C2 (NPC2) protein has been characterized as a cholesterol-binding protein. Its loss leads to NPC2 disease, an inherited neurodegenerative disorder. When analyzing gene expression profile, we noticed high expression of both NPC2 and its receptor, mannose 6-phosphate receptor (MPR), in murine hematopoietic stem cells. NPC2 protein, in the presence of thrombopoietin (TPO), causes an increase in CFU-GEMM (colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte) and a decrease in CFU-GM (colony-forming unit-granulocyte-macrophage) colony number in colony-forming cell (CFC) assays. This effect is independent of cholesterol binding but does require the presence of MPR. With M07e cells, a TPO-dependent hematopoietic leukemia cell line, NPC2 can inhibit TPO-induced differentiation and enhance TPO-mediated anti-apoptosis effects. Strikingly, these results are not observed under the standard 20% O2 level of the standard incubator, but rather at 7% O2, the physiological oxygen level of bone marrow. Furthermore, NPC2 protein upregulates hypoxia inducible factor 1-α protein level at 7% O2, but not at 20% O2. Our results demonstrate that NPC2 protein plays a role in hematopoiesis at the physiologic bone marrow level of O2.
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Research Interests: Microbiology, Medical Microbiology, Extracellular Matrix, Cell line, Humans, and 17 moreSensorineural Hearing Loss, Infectious Disease, Mice, Animals, Male, Inner Ear, Clinical Sciences, Rats, Monocytes, Otitis Media, Temporal Bone, Labyrinthitis, Haemophilus Infections Market, Tympanic Membrane, Gene Expression Regulation, Haemophilus influenzae, and fibroblasts
Research Interests: Toll like receptor signaling, Biological Sciences, High Frequency, Infection and immunity, Cell line, and 18 moreHumans, Sensorineural Hearing Loss, Mice, Animals, Male, NF-kappa B, Hearing Loss, Inner Ear, Rats, Otitis Media, Chronic Otitis Media, Ligaments, Monocyte Chemotactic Protein-1, Spiral Ganglion, Haemophilus influenzae, Acute Disease, Child preschool, and fibroblasts
We investigated the effects of low-intensity ultrasound (LIUS) on the activity of human articular chondrocytes isolated from osteoarthritis patients and cultured in the three-dimensional alginate beads. LIUS was treated at 0, 100, 200,... more
We investigated the effects of low-intensity ultrasound (LIUS) on the activity of human articular chondrocytes isolated from osteoarthritis patients and cultured in the three-dimensional alginate beads. LIUS was treated at 0, 100, 200, and 300 mW/cm2 for 10 min everyday for 2, 7, or 15 days. LIUS induced the viability of cells only at day 15 but not until day 7 after treatment, when examined by trypan blue exclusion and LIVE/DEAD® assay kit. When examined at day 7, the proliferation of cells was not changed by LIUS in the 3H-thymine incorporation. The expression of matrix producing proteins (type II collagen and proteoglycan) was clearly induced by 200–300 mW/cm2 LIUS in the incorporation of radioactivity and Northern blot analysis. Although the expression of MMP-1, a matrix degrading protein, was decreased, that of TIMP-1, an inhibitor of MMPs, was not affected by LIUS. Histological analysis revealed an increase in the number and size of glycosaminoglycan-positive lacunae and cellular organelles, appearing as rough endoplasmic reticulum and mitochondria by LIUS. These results showed that the viability and metabolism of human articular chondrocytes in alginate culture was induced by LIUS treatment, suggesting that they could be a promising autologous source for cartilage tissue engineering. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006