The Protective Effects of Parathyroid Hormone (1-34) on Cartilage and Subchondral Bone Through Down-Regulating JAK2/STAT3 and WNT5A/ROR2 in a Collagenase-Induced Osteoarthritis Mouse Model.
Orthop Surg
; 13(5): 1662-1672, 2021 Jul.
Article
in En
| MEDLINE
| ID: mdl-34105258
ABSTRACT
OBJECTIVE:
To assess the effects of PTH (1-34) on bone and cartilage metabolism in a collagenase-induced mouse model of osteoarthritis (OA) and examine whether PTH (1-34) affects the expression of JAK2/STAT3 and WNT5A/ROR2 in this process.METHODS:
Eighteen 12-week-old male C57Bl/6 mice were randomly assigned into three groups as follows sham group (Group A), the collagenase + saline injection group (Group B), and the collagenase + PTH (1-34) treatment group (Group C). Collagenase was injected (intra-articular) into the knee joint of Group B and C. The PTH (1-34)-treatment was started at 6 weeks after the operation and lasted for 6 weeks. Cartilage pathology was evaluated by gross visual, histological, and immunohistochemical assessments. Subchondral bone was evaluated by microcomputed tomography (micro-CT) and immunohistochemical analyses.RESULTS:
The OARSI macroscopic and microscopic scores of Group B were higher than those of Group A (P = 0.026; P = 0.002, respectively). Group C showed statistically significant differences in macroscopic and microscopic scores from Group B (P = 0.041; P = 0.008, respectively). The results showed that the Col-II and AGG expression levels in the cartilage tissue were significantly lower in Group B than Group A (P < 0.001; P = 0.008, respectively). The Col-II and AGG expression levels were significantly higher in Group C than Group B (P = 0.009; P = 0.014, respectively). MMP-13, ADAMTS-4, Caspase-3, P53, and Bax expression levels were significantly higher in Group B than the Group A (P < 0.001; P < 0.001; P = 0.04; P < 0.001; P = 0.005, respectively); however, the cartilage tissue in Group C showed significantly less ADAMTS-4, MMP-13, Caspase-3, P53, and Bax expression than Group B (P < 0.001, P < 0.001, P = 0.044; P = 0.002; P = 0.005, respectively). Over-expressed JAK2/STAT3 and WNT5A/ROR2 were observed in both cartilage and subchondral bone in this model; however, these changes were prevented by PTH (1-34) treatment. These parameters (bone mineral density, bone volume ratio, trabecular bone pattern factor, and structure model index) of micro-CT indicated subchondral bone loss and architecture changes in Group B, but improvements in these parameters in Group C.CONCLUSIONS:
PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a collagenase-induced OA mouse model, and it may be involved in down-regulating the expression of JAK2/STAT3 and WNT5A/ROR2.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parathyroid Hormone
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Cartilage, Articular
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Osteoarthritis, Knee
/
STAT3 Transcription Factor
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Janus Kinase 2
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Receptor Tyrosine Kinase-like Orphan Receptors
/
Wnt-5a Protein
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Orthop Surg
Year:
2021
Document type:
Article
Affiliation country:
China