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
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-07-01
|
| Series: | Orthopaedic Surgery |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/os.13019 |
| _version_ | 1818453430628253696 |
|---|---|
| author | Li‐tao Shao Yu Gou Jia‐kang Fang Yun‐peng Hu Qiang‐qiang Lian Zhou Yang Yu‐ying Zhang Yu‐dan Wang Fa‐ming Tian Liu Zhang |
| author_facet | Li‐tao Shao Yu Gou Jia‐kang Fang Yun‐peng Hu Qiang‐qiang Lian Zhou Yang Yu‐ying Zhang Yu‐dan Wang Fa‐ming Tian Liu Zhang |
| author_sort | Li‐tao Shao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T21:38:52Z |
| format | Article |
| id | doaj.art-8a2a7050554948dead0f4817082bb1d6 |
| institution | Directory Open Access Journal |
| issn | 1757-7853 1757-7861 |
| language | English |
| last_indexed | 2024-12-14T21:38:52Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Orthopaedic Surgery |
| spelling | doaj.art-8a2a7050554948dead0f4817082bb1d62022-12-21T22:46:31ZengWileyOrthopaedic Surgery1757-78531757-78612021-07-011351662167210.1111/os.13019The 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 ModelLi‐tao Shao0Yu Gou1Jia‐kang Fang2Yun‐peng Hu3Qiang‐qiang Lian4Zhou Yang5Yu‐ying Zhang6Yu‐dan Wang7Fa‐ming Tian8Liu Zhang9Department of Orthopedic Surgery Hebei Medical University Shijiazhuang ChinaDepartment of Orthopedic Surgery Tianjin Hospital, Tianjin University Tianjin ChinaMedical Research Center Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology Tangshan ChinaMedical Research Center Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology Tangshan ChinaMedical Research Center Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology Tangshan ChinaMedical Research Center Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology Tangshan ChinaMedical Research Center Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology Tangshan ChinaMedical Research Center Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology Tangshan ChinaMedical Research Center Hebei Key Laboratory for Organ Fibrosis, North China University of Science and Technology Tangshan ChinaDepartment of Orthopedic Surgery Hebei Medical University Shijiazhuang ChinaObjective 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.https://doi.org/10.1111/os.13019CartilageJAK2OsteoarthritisParathyroid hormoneSubchondral bone |
| spellingShingle | Li‐tao Shao Yu Gou Jia‐kang Fang Yun‐peng Hu Qiang‐qiang Lian Zhou Yang Yu‐ying Zhang Yu‐dan Wang Fa‐ming Tian Liu Zhang 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 Orthopaedic Surgery Cartilage JAK2 Osteoarthritis Parathyroid hormone Subchondral bone |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Cartilage JAK2 Osteoarthritis Parathyroid hormone Subchondral bone |
| url | https://doi.org/10.1111/os.13019 |
| work_keys_str_mv | AT litaoshao theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yugou theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT jiakangfang theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yunpenghu theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT qiangqianglian theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT zhouyang theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yuyingzhang theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yudanwang theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT famingtian theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT liuzhang theprotectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT litaoshao protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yugou protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT jiakangfang protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yunpenghu protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT qiangqianglian protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT zhouyang protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yuyingzhang protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT yudanwang protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT famingtian protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel AT liuzhang protectiveeffectsofparathyroidhormone134oncartilageandsubchondralbonethroughdownregulatingjak2stat3andwnt5aror2inacollagenaseinducedosteoarthritismousemodel |