Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway
Abstract Background To determine if ipriflavone, a novel and safe inhibitor of Indian hedgehog (Ihh) signaling, can attenuate cartilage degeneration by blocking the Ihh pathway. Methods Human chondrocytes were used to evaluate Ihh signaling, cell proliferation, apoptosis, gene, and protein expressio...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-05-01
|
| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-019-1895-x |
| _version_ | 1818486398184849408 |
|---|---|
| author | Li Guo Xiaochun Wei Zhiwei Zhang Xiaojian Wang Chunli Wang Pengcui Li Chunfang Wang Lei Wei |
| author_facet | Li Guo Xiaochun Wei Zhiwei Zhang Xiaojian Wang Chunli Wang Pengcui Li Chunfang Wang Lei Wei |
| author_sort | Li Guo |
| collection | DOAJ |
| description | Abstract Background To determine if ipriflavone, a novel and safe inhibitor of Indian hedgehog (Ihh) signaling, can attenuate cartilage degeneration by blocking the Ihh pathway. Methods Human chondrocytes were used to evaluate Ihh signaling, cell proliferation, apoptosis, gene, and protein expression of chondrocytes by cell proliferation and apoptosis assays, real-time qPCR, and Western blotting at 48 h after ipriflavone treatment. Human cartilage explants were further used to validate the cell culture results. The effects of ipriflavone on cartilage degeneration in vivo were assessed using the rat ACLT OA model. Two-month-old male SD rats were randomized into 3 groups (n = 75): (1) sham, (2) ACLT alone, and (3) ACLT+ ipriflavone. Ipriflavone was administered intragastrically at 24 h after ACLT for 6 weeks. The extent of OA progression was evaluated by the OARSI score and immunohistochemistry at 12 weeks after surgery. The Ihh signaling pathway and OA-related genes were quantified by real-time PCR. Results Cell proliferation in the cells treated with ipriflavone was increased to 36.40% ± 1.32% (5 μM) and 28.54% ± 0.74% (10 μM) from 11.99% ± 0.35% (DMSO) (P < 0.001), and apoptosis was decreased to 12.64% ± 3.7% (5 μM) and 15.18% ± 3.13% (10 μM) from 25.76% ± 5.1% (DMSO) (P < 0.05). Ipriflavone blocked Runx-2 mainly through the Smo-Gli2 pathway. A similar result was found in the cartilage explant culture. Ihh signaling in vivo was inhibited in animals treated with ipriflavone. Safranin-O staining revealed a less cartilage damage with lower OARSI scores (P < 0.05) in the ipriflavone-treated animals compared with untreated animals. The gene expression of Smo and Gli2 was inhibited significantly by ipriflavone (P < 0.05). The OA-related gene and protein type X, MMP-13, and type II collagen-C fragment were reduced, while type II collagen and Agg were increased in the ipriflavone-treated animals (P < 0.05). Conclusions Catabolic genes were disrupted by blocking the Ihh pathway. This finding suggests that disruption of Ihh signaling with ipriflavone provides chondral protection in rat posttraumatic OA. |
| first_indexed | 2024-12-10T16:22:25Z |
| format | Article |
| id | doaj.art-39949a9226784a99b74d53d5790052ff |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-10T16:22:25Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-39949a9226784a99b74d53d5790052ff2022-12-22T01:41:46ZengBMCArthritis Research & Therapy1478-63622019-05-0121111210.1186/s13075-019-1895-xIpriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathwayLi Guo0Xiaochun Wei1Zhiwei Zhang2Xiaojian Wang3Chunli Wang4Pengcui Li5Chunfang Wang6Lei Wei7Department of Orthopedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury RepairDepartment of Orthopedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury RepairDepartment of Orthopedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury RepairDepartment of Orthopedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury RepairDepartment of Orthopedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury RepairDepartment of Orthopedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury RepairShanxi Key Laboratory of Laboratory Animal and Animal Model of Human Diseases, Department of Experimental Animal Center, Shanxi Medical UniversityDepartment of Orthopedics, Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury RepairAbstract Background To determine if ipriflavone, a novel and safe inhibitor of Indian hedgehog (Ihh) signaling, can attenuate cartilage degeneration by blocking the Ihh pathway. Methods Human chondrocytes were used to evaluate Ihh signaling, cell proliferation, apoptosis, gene, and protein expression of chondrocytes by cell proliferation and apoptosis assays, real-time qPCR, and Western blotting at 48 h after ipriflavone treatment. Human cartilage explants were further used to validate the cell culture results. The effects of ipriflavone on cartilage degeneration in vivo were assessed using the rat ACLT OA model. Two-month-old male SD rats were randomized into 3 groups (n = 75): (1) sham, (2) ACLT alone, and (3) ACLT+ ipriflavone. Ipriflavone was administered intragastrically at 24 h after ACLT for 6 weeks. The extent of OA progression was evaluated by the OARSI score and immunohistochemistry at 12 weeks after surgery. The Ihh signaling pathway and OA-related genes were quantified by real-time PCR. Results Cell proliferation in the cells treated with ipriflavone was increased to 36.40% ± 1.32% (5 μM) and 28.54% ± 0.74% (10 μM) from 11.99% ± 0.35% (DMSO) (P < 0.001), and apoptosis was decreased to 12.64% ± 3.7% (5 μM) and 15.18% ± 3.13% (10 μM) from 25.76% ± 5.1% (DMSO) (P < 0.05). Ipriflavone blocked Runx-2 mainly through the Smo-Gli2 pathway. A similar result was found in the cartilage explant culture. Ihh signaling in vivo was inhibited in animals treated with ipriflavone. Safranin-O staining revealed a less cartilage damage with lower OARSI scores (P < 0.05) in the ipriflavone-treated animals compared with untreated animals. The gene expression of Smo and Gli2 was inhibited significantly by ipriflavone (P < 0.05). The OA-related gene and protein type X, MMP-13, and type II collagen-C fragment were reduced, while type II collagen and Agg were increased in the ipriflavone-treated animals (P < 0.05). Conclusions Catabolic genes were disrupted by blocking the Ihh pathway. This finding suggests that disruption of Ihh signaling with ipriflavone provides chondral protection in rat posttraumatic OA.http://link.springer.com/article/10.1186/s13075-019-1895-xIpriflavoneOsteoarthritisIndian hedgehogChondrocyte hypertrophy |
| spellingShingle | Li Guo Xiaochun Wei Zhiwei Zhang Xiaojian Wang Chunli Wang Pengcui Li Chunfang Wang Lei Wei Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway Arthritis Research & Therapy Ipriflavone Osteoarthritis Indian hedgehog Chondrocyte hypertrophy |
| title | Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway |
| title_full | Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway |
| title_fullStr | Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway |
| title_full_unstemmed | Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway |
| title_short | Ipriflavone attenuates the degeneration of cartilage by blocking the Indian hedgehog pathway |
| title_sort | ipriflavone attenuates the degeneration of cartilage by blocking the indian hedgehog pathway |
| topic | Ipriflavone Osteoarthritis Indian hedgehog Chondrocyte hypertrophy |
| url | http://link.springer.com/article/10.1186/s13075-019-1895-x |
| work_keys_str_mv | AT liguo ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway AT xiaochunwei ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway AT zhiweizhang ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway AT xiaojianwang ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway AT chunliwang ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway AT pengcuili ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway AT chunfangwang ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway AT leiwei ipriflavoneattenuatesthedegenerationofcartilagebyblockingtheindianhedgehogpathway |