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Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis
- Source :
- Annals of the Rheumatic Diseases
- Publication Year :
- 2013
-
Abstract
- Background Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). Objectives To investigate the analgesic potential of a modified version of osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) in the monosodium iodoacetate (MIA) model of OA pain. Methods Male Sprague Dawley rats (140–260 g) were treated with either OPG-Fc (3 mg/kg, subcutaneously) or vehicle (phosphate-buffered saline) between days 1 and 27 (pre-emptive treatment) or days 21 and 27 (therapeutic treatment) after an intra-articular injection of MIA (1 mg/50 ml) or saline. A separate cohort of rats received the bisphosphonate zoledronate (100 mg/kg, subcutaneously) between days 1 and 25 post-MIA injection. Incapacitance testing and von Frey (1–15 g) hind paw withdrawal thresholds were used to assess pain behaviour. At the end of the study, rats were killed and the knee joints and spinal cord removed for analysis. Immunohistochemical studies using Iba-1 and GFAP quantified levels of activation of spinal microglia and astrocytes, respectively. Joint sections were stained with haematoxylin and eosin or Safranin-O fast green and scored for matrix proteoglycan and overall joint morphology. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts were quantified. N=10 rats/group. Results Pre-emptive treatment with OPG-Fc significantly attenuated the development of MIA-induced changes in weightbearing, but not allodynia. OPG-Fc decreased osteoclast number, inhibited the formation of osteophytes and improved structural pathology within the joint similarly to the decrease seen after pretreatment with the bisphosphonate, zoledronate. Therapeutic treatment with OPG-Fc decreased pain behaviour, but did not improve pathology in rats with established joint damage. Conclusions Our data suggest that early targeting of osteoclasts may reduce pain associated with OA.
- Subjects :
- musculoskeletal diseases
Male
Pathology
medicine.medical_specialty
medicine.medical_treatment
Immunology
Analgesic
Osteoclasts
Osteoarthritis
Zoledronic Acid
General Biochemistry, Genetics and Molecular Biology
Bone remodeling
Rats, Sprague-Dawley
Knee Osteoarthritis
Rheumatology
Osteoprotegerin
Osteoclast
Synovitis
Immunology and Allergy
Medicine
Animals
Enzyme Inhibitors
Basic and Translational Research
Behavior, Animal
Bone Density Conservation Agents
Diphosphonates
business.industry
Imidazoles
Osteophyte
Nociceptors
Bisphosphonate
medicine.disease
Arthralgia
Iodoacetic Acid
Rats
Disease Models, Animal
Allodynia
medicine.anatomical_structure
Spinal Cord
Drug Design
Joints
Bone Remodeling
medicine.symptom
business
Subjects
Details
- ISSN :
- 14682060
- Volume :
- 73
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Annals of the rheumatic diseases
- Accession number :
- edsair.doi.dedup.....b4ce63fea1128752fe029106393a6961