title: Aspartic acid racemization reveals a high turnover state in knee compared with hip osteoarthritic cartilage.
abstract: OBJECTIVE
  We investigated tissue turnover in healthy and osteoarthritic cartilage. We challenge long held views that osteoarthritis (OA) is dominated by a similar turnover process in all joints and present evidence that hip and knee cartilage respond very differently to OA.
  
  
  METHODS
  d- and l-Aspartate (Asp) were quantified for whole cartilage, collagen and non-collagenous components of cartilage obtained at the time of joint replacement. We computed the Asp racemization ratio (Asp-RR = d/d + l Asp), reflecting the proportion of old to total protein, for each component.
  
  
  RESULTS
  Compared with hip OA, knee OA collagen fibrils (P < 0.0001), collagen (P = 0.007), and non-collagenous proteins (P = 0.0003) had significantly lower age-adjusted mean Asp-RRs consistent with elevated protein synthesis in knee OA. Knee OA collagen had a mean hydroxyproline/proline (H/P) ratio of 1.2 consistent with the presence of type III collagen whereas hip OA collagen had a mean H/P ratio of 0.99 consistent with type II collagen. Based on Asp-RR, the relative age was significantly different in knee and hip OA (P < 0.0005); on average OA knees were estimated to be 30 yrs 'younger', and OA hips 10 yrs 'older' than non-OA.
  
  
  CONCLUSIONS
  The metabolic response to OA was strikingly different by joint site. Knee OA cartilage evinced an anabolic response that appeared to be absent in hip OA cartilage. These results challenge the long held view that OA cartilage is capable of only minimal repair and that collagen loss is irreversible.
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: jcatterall@gmail.com.
authors.forename: J B
authors.initials: JB
authors.lastname: Catterall
authors.affiliation: Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Zura
authors.affiliation: Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Bolognesi
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA; Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: V B
authors.initials: VB
authors.lastname: Kraus
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001224:Aspartic Acid / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D026603:D-Aspartic Acid / Q000378:metabolism*; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D055815:Young Adult
chemical_list: D024043:Collagen Type II; D024061:Collagen Type III; D001224:Aspartic Acid; D026603:D-Aspartic Acid; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline
keywords: Cartilage turnover; Collagen; Osteoarthritis; Racemization