title: Del1 Knockout Mice Developed More Severe Osteoarthritis Associated with Increased Susceptibility of Chondrocytes to Apoptosis.
abstract: OBJECTIVE
  We identified significant expression of the matricellular protein, DEL1, in hypertrophic and mature cartilage during development. We hypothesized that this tissue-specific expression indicated a biological role for DEL1 in cartilage biology.
  
  
  METHODS
  Del1 KO and WT mice had cartilage thickness evaluated by histomorphometry. Additional mice underwent medial meniscectomy to induce osteoarthritis, and were assayed at 1 week for apoptosis by TUNEL staining and at 8 weeks for histology and OA scoring. In vitro proliferation and apoptosis assays were performed on primary chondrocytes.
  
  
  RESULTS
  Deletion of the Del1 gene led to decreased amounts of cartilage in the ears and knee joints in mice with otherwise normal skeletal morphology. Destabilization of the knee led to more severe OA compared to controls. In vitro, DEL1 blocked apoptosis in chondrocytes.
  
  
  CONCLUSIONS
  Osteoarthritis is among the most prevalent diseases worldwide and increasing in incidence as our population ages. Initiation begins with an injury resulting in the release of inflammatory mediators. Excessive production of inflammatory mediators results in apoptosis of chondrocytes. Because of the limited ability of chondrocytes to regenerate, articular cartilage deteriorates leading to the clinical symptoms including severe pain and decreased mobility. No treatments effectively block the progression of OA. We propose that direct modulation of chondrocyte apoptosis is a key variable in the etiology of OA, and therapies aimed at preventing this important step represent a new class of regenerative medicine targets.
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Zhen
authors: Z
authors: Wang
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Misha C
authors: MC
authors: Tran
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Namrata J
authors: NJ
authors: Bhatia
authors: Department of Materials Science and Engineering, Stanford University, Stanford, CA, United States of America.
authors: Alexander W
authors: AW
authors: Hsing
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Carol
authors: C
authors: Chen
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Marie F
authors: MF
authors: LaRussa
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Ernst
authors: E
authors: Fattakhov
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Vania
authors: V
authors: Rashidi
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.|Department of Pathology, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors: Kyu Yun
authors: KY
authors: Jang
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Kevin J
authors: KJ
authors: Choo
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Xingju
authors: X
authors: Nie
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Jonathan A
authors: JA
authors: Mathy
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Michael T
authors: MT
authors: Longaker
authors: Department of Materials Science and Engineering, Stanford University, Stanford, CA, United States of America.
authors: Reinhold H
authors: RH
authors: Dauskardt
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.
authors: Jill A
authors: JA
authors: Helms
authors: Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States of America.|Palo Alto VA Health Care System, Palo Alto, CA, United States of America.
authors: George P
authors: GP
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002356:Cartilage / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules; D019902:Chondrocytes / Q000473:pathology*; D004198:Disease Susceptibility; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger