title: IL-3 Decreases Cartilage Degeneration by Downregulating Matrix Metalloproteinases and Reduces Joint Destruction in Osteoarthritic Mice.
abstract: Osteoarthritis (OA) is a chronic disease of articular joints that leads to degeneration of both cartilage and subchondral bone. These degenerative changes are further aggravated by proinflammatory cytokines including IL-1β and TNF-α. Previously, we have reported that IL-3, a cytokine secreted by activated T cells, protects cartilage and bone damage in murine models of inflammatory and rheumatoid arthritis. However, how IL-3 protects cartilage degeneration is not yet known. In this study, we investigated the role of IL-3 on cartilage degeneration under both in vitro and in vivo conditions. We found that both mouse and human chondrocytes show strong expression of IL-3R at gene and protein levels. IL-3 increases the expression of mouse chondrocyte-specific genes, Sox9 and collagen type IIa, which were downregulated by IL-1β. Moreover, IL-3 downregulated IL-1β- and TNF-α-induced expression of matrix metalloproteinases in both mouse and human chondrocytes. Interestingly, IL-3 reduces the degeneration of articular cartilage and subchondral bone microarchitecture in a mouse model of human OA. Moreover, IL-3 showed the preventive and therapeutic effects on cartilage degeneration induced by IL-1β in micromass pellet cultures of human mesenchymal stem cells. Thus, to our knowledge, we provide the first evidence that IL-3 has therapeutic potential in amelioration of degeneration of articular cartilage and subchondral bone microarchitecture associated with OA.
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411007, India;
authors.forename: Supinder
authors.identifier: 0000-0003-0866-7267
authors.initials: S
authors.lastname: Kour
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411007, India;
authors.forename: Manasa G
authors.initials: MG
authors.lastname: Garimella
authors.affiliation: Department of Veterinary Surgery, Krantisinh Nana Patil College of Veterinary Science, Shirwal 412801, Satara, India;
authors.forename: Divya A
authors.identifier: 0000-0001-9085-5675
authors.initials: DA
authors.lastname: Shiroor
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411007, India;
authors.forename: Suhas T
authors.identifier: 0000-0002-5672-1355
authors.initials: ST
authors.lastname: Mhaske
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411007, India;
authors.forename: Snehal R
authors.initials: SR
authors.lastname: Joshi
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411007, India;
authors.forename: Kanupriya
authors.identifier: 0000-0003-3511-1459
authors.initials: K
authors.lastname: Singh
authors.affiliation: Division of Endocrinology, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow 226031, India; and.
authors.forename: Subhashis
authors.initials: S
authors.lastname: Pal
authors.affiliation: Division of Endocrinology, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow 226031, India; and.
authors.forename: Monika
authors.initials: M
authors.lastname: Mittal
authors.affiliation: Department of Orthopaedic Surgery, Armed Forces Medical College, Pune 411040, India.
authors.forename: Hari B
authors.identifier: 0000-0001-7901-8569
authors.initials: HB
authors.lastname: Krishnan
authors.affiliation: Division of Endocrinology, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow 226031, India; and.
authors.forename: Naibedya
authors.identifier: 0000-0003-2473-0246
authors.initials: N
authors.lastname: Chattopadhyay
authors.affiliation: Department of Veterinary Surgery, Krantisinh Nana Patil College of Veterinary Science, Shirwal 412801, Satara, India;
authors.forename: Anil H
authors.initials: AH
authors.lastname: Ulemale
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411007, India; mohanwani@nccs.res.in.
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Wani
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000276:immunology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007377:Interleukin-3 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053650:Interleukin-3 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D024043:Collagen Type II; C115022:IL3RA protein, human; D053583:Interleukin-1beta; D007377:Interleukin-3; D053650:Interleukin-3 Receptor alpha Subunit; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases