title: PTHrP overexpression partially inhibits a mechanical strain-induced arthritic phenotype in chondrocytes.
abstract: OBJECTIVE
  Cell-based tissue engineering strategies are currently in clinical use and continue to be developed at a rapid pace for the repair of cartilage defects. Regardless of the repair methodology, chondrocytes within newly regenerated cartilage remain susceptible to the abnormal inflammatory and mechanical environments that underlie osteoarthritic disease, likely compromising the implant's integration, function, and longevity. The present study investigates the use of parathyroid hormone-related peptide (PTHrP) overexpression for chondroprotection.
  
  
  METHODS
  Bovine articular chondrocytes were transfected with human PTHrP (hPTHrP) constructs (1-141 or 1-173) and subjected to injurious cyclic tensile strain (CTS; 0.5 Hz and 16% elongation) for 48 h. mRNA expression of matrix remodeling, inflammatory signaling, hypertrophic, and apoptotic genes were examined with real-time reverse transcription polymerase chain reaction. Nitric oxide (NO) and prostaglandin E₂ (PGE₂) production were measured using the Griess assay and enzyme immunoassay (EIA), respectively.
  
  
  RESULTS
  CTS-induced an arthritic phenotype in articular chondrocytes as indicated by increased gene expression of collagenases and aggrecanases and increased production of NO and PGE₂. Additionally, CTS increased collagen type X (Col10a1) mRNA expression, whereas overexpression of either hPTHrP isoform inhibited CTS-induced Col10a1 gene expression. However, hPTHrP 1-141 augmented CTS-induced NO and PGE₂ production, and neither hPTHrP isoform had any significant effect on apoptotic genes.
  
  
  CONCLUSIONS
  Our results suggest that chondrocytes overexpressing PTHrP resist mechanical strain-induced hypertrophic-like changes. Therapeutic PTHrP gene transfer may be considered for chondroprotection applications in newly regenerated cartilage.
authors.affiliation: Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services Bethesda, MD 20892, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: J M
authors.initials: JM
authors.lastname: Taboas
authors.forename: R S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D005786:Gene Expression Regulation; D009569:Nitric Oxide / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D014162:Transfection
chemical_list: D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D009569:Nitric Oxide; D015232:Dinoprostone