title: Different doses of strontium ranelate and mechanical vibration modulate distinct responses in the articular cartilage of ovariectomized rats.
abstract: To investigate the effects of different strontium ranelate (SrR) doses alone or in combination with low-intensity and high-frequency mechanical vibration (MV) on articular cartilage in ovariectomized rats.
  
  
  
  Fifty 6-month-old female Wistar rats underwent ovariectomy (OVX) and after 3 months were divided into: control group (Control); SrR 300 mg/kg/day (SrR300); SrR 625 mg/kg/day (SrR625); MV; SrR 625 mg/kg/day plus MV (SrR625 + MV). The vehicle and the SrR were administered by gavage 7 days/week and vibration (0.6 g/60 Hz) was performed for 20 min/day, 5 days/week. Bone mineral density (BMD) and body composition were evaluated by densitometry. Changes in cartilage were assessed 90 days after treatment by histomorphometry; immunohistochemistry analysis evaluating cell death (caspase-3), tumor necrosis factor-α (TNF-α), metalloproteinase 9 (MMP-9) and type II collagen; Osteoarthritis Research Society International (OARSI) grading system and glycosaminoglycans (GAGs) analyses.
  
  
  
  SrR-treated groups exhibited a lower OARSI grade, a smaller number of chondrocyte clusters, increased levels of chondroitin sulfate (CS) and decreased expression of caspase-3. Additionally, compared to all the groups, SrR300 exhibited increased levels of hyaluronic acid (HA). Vibration applied alone or in combination accelerated cartilage degradation, as demonstrated by increased OARSI grade, reduced number of chondrocytes, increased number of clusters, elevated expression of type II collagen and cell death, and was accompanied by decreased amounts of CS and HA; however, MV alone was able to reduce MMP-9.
  
  
  
  SrR and vibration modulate distinct responses in cartilage. Combined treatment accelerates degeneration. In contrast, SrR treatment at 300 mg/kg/day attenuates osteoarthritis (OA) progression, improving cartilage matrix quality and preserving cell viability in ovariectomized rats.
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: hidalgomierzwa@gmail.com.
authors.forename: A G H
authors.initials: AGH
authors.lastname: Mierzwa
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: jeniferfc.bio@gmail.com.
authors.forename: J F
authors.initials: JF
authors.lastname: Campos
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: mariana.fj82@gmail.com.
authors.forename: M F
authors.initials: MF
authors.lastname: Jesus
authors.affiliation: Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: hbnader.bioq@epm.br.
authors.forename: H B
authors.initials: HB
authors.lastname: Nader
authors.affiliation: Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: lazaretti.castro@unifesp.br.
authors.forename: M
authors.initials: M
authors.lastname: Lazaretti-Castro
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: rejanedr.morf@epm.br.
authors.forename: R D
authors.initials: RD
authors.lastname: Reginato
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002357:Cartilage Diseases / Q000139:chemically induced; D002358:Cartilage, Articular / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D019902:Chondrocytes / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006614:Hindlimb / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014732:Vibration
chemical_list: D050071:Bone Density Conservation Agents; D006025:Glycosaminoglycans; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; C081587:strontium ranelate; D006820:Hyaluronic Acid; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9
keywords: Articular cartilage; Cartilage matrix; Mechanical vibration; Osteoarthritis; Ovariectomized rats; Strontium ranelate