title: Beneficial effects of natural eggshell membrane (NEM) on multiple indices of arthritis in collagen-induced arthritic rats.
abstract: OBJECTIVE
  This study was performed to evaluate the potential efficacy of natural eggshell membrane (NEM) in collagen-induced arthritic rats, a well-established rodent model of inflammation and rheumatoid arthritis.
  
  
  METHODS
  Rats with developing type II collagen-induced arthritis (CIA) were treated once daily by oral gavage on study days -14 to 17 with vehicle or NEM (52 mg/kg body weight). Rats were euthanized on study day 17. Efficacy was assessed by daily ankle caliper measurements, ankle diameter expressed as area under the curve (AUCd0-17), and histopathologic evaluation of ankles and knees. Serum biomarkers of cartilage function and inflammation [collagen type II C-telopeptide (CTXII), cartilage oligomeric matrix protein (COMP), and alpha-2-macroglobulin (A2M)] were measured by ELISA.
  
  
  RESULTS
  Treatment with NEM resulted in significant beneficial effects on the daily ankle diameter measurements and ankle diameter AUC. Ankle and knee histopathology scores were significantly reduced (36% and 43% reduction of summed individual histopathology scores for ankle and knee, respectively; p < 0.05) toward normal for rats given NEM compared to vehicle controls. The percent reduction of serum CTXII, COMP, and A2M in NEM-treated rats ranged from 30% to 72% (p < 0.05).
  
  
  CONCLUSIONS
  NEM significantly improved multiple aspects of inflammatory arthritis including inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation. This study provides further support for the use of CTXII, COMP, and A2M as relevant biomarkers that were responsive to NEM.
authors.affiliation: a Research and Development Department , Novus International , St. Charles , MO , USA.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Wedekind
authors.affiliation: b ESM Technologies, LLC , Carthage , MO , USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Ruff
authors.affiliation: a Research and Development Department , Novus International , St. Charles , MO , USA.
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Atwell
authors.affiliation: c P and N Development Ventures , St. Louis , MO , USA , and.
authors.forename: Joseph L
authors.identifier: http://orcid.org/0000-0002-9334-1650
authors.initials: JL
authors.lastname: Evans
authors.affiliation: d Bolder BioPATH, Inc. , Boulder , CO , USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Bendele
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001688:Biological Products / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D064236:Cartilage Oligomeric Matrix Protein / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D004528:Egg Shell; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D051381:Rats; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D050071:Bone Density Conservation Agents; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D010446:Peptide Fragments; C543437:collagen II C-telopeptide
keywords: A2M; COMP; CTXII; Methotrexate; Rheumatoid