Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence
Background/objective: As the pivotal cellular mediators of bone resorption and pathological bone remodeling, osteoclasts have emerged as a prominent target for anti-resorptive interventions. Pinocembrin (PIN), a predominant flavonoid found in damiana, honey, fingerroot, and propolis, has been recogn...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Journal of Orthopaedic Translation |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X24000032 |
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| author | Guoju Hong Shuqiang Li Guanqiang Zheng Xiaoxia Zheng Qunzhang Zhan Lin Zhou Qiushi Wei Wei He Zhenqiu Chen |
| author_facet | Guoju Hong Shuqiang Li Guanqiang Zheng Xiaoxia Zheng Qunzhang Zhan Lin Zhou Qiushi Wei Wei He Zhenqiu Chen |
| author_sort | Guoju Hong |
| collection | DOAJ |
| description | Background/objective: As the pivotal cellular mediators of bone resorption and pathological bone remodeling, osteoclasts have emerged as a prominent target for anti-resorptive interventions. Pinocembrin (PIN), a predominant flavonoid found in damiana, honey, fingerroot, and propolis, has been recognized for its potential therapeutic effects in osteolysis. The purpose of our project is to investigate the potential of PIN to prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms. Methods: The study commenced by employing protein-ligand molecular docking to ascertain the specific interaction between PIN and nuclear factor-κB (NF-κB) ligand (RANKL). Subsequently, PIN was introduced to bone marrow macrophages (BMMs) under the stimulation of RANKL. The impact of PIN on osteoclastic activity was assessed through the utilization of a positive TRAcP staining kit and a hydroxyapatite resorption assay. Furthermore, the study investigated the generation of reactive oxygen species (ROS) in osteoclasts induced by RANKL using H2DCFDA. To delve deeper into the underlying mechanisms, molecular cascades triggered by RANKL, including NF-κB, ROS, calcium oscillations, and NFATc1-mediated signaling pathways, were explored using Luciferase gene report, western blot analysis, and quantitative real-time polymerase chain reaction. Moreover, an estrogen-deficient osteoporosis murine model was established to evaluate the therapeutic effects of PIN in vivo. Results: In this study, we elucidated the profound inhibitory effects of PIN on osteoclastogenesis and bone resorption, achieved through repression of NF-κB and NFATc1-mediated signaling pathways. Notably, PIN also exhibited potent anti-oxidative properties by mitigating RANKL-induced ROS generation and augmenting activities of ROS-scavenging enzymes, ultimately leading to a reduction in intracellular ROS levels. Moreover, PIN effectively abrogated the expression of osteoclast-specific marker genes (Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-fos, and Mmp9), further underscoring its inhibitory impact on osteoclast differentiation and function. Additionally, employing an in vivo mouse model, we demonstrated that PIN effectively prevented osteoclast-induced bone loss resultant from estrogen deficiency. Conclusion: Our findings highlight the potent inhibitory effects of PIN on osteoclastogenesis, bone resorption, and RANKL-induced signaling pathways, thereby establishing PIN as a promising therapeutic candidate for the prevention and management of osteolytic bone diseases. The translational potential of this article: PIN serves as a promising therapeutic agent for the prevention and management of osteolytic bone diseases and holds promise for future clinical applications in addressing conditions characterized by excessive bone resorption. PIN is a natural compound found in various sources, including damiana, honey, fingerroot, and propolis. Its widespread availability and potential for therapeutic use make it an attractive candidate for further investigation and development as a clinical intervention. |
| first_indexed | 2024-04-24T07:58:38Z |
| format | Article |
| id | doaj.art-cd08d340fbd546ed986c17ae2840ad9b |
| institution | Directory Open Access Journal |
| issn | 2214-031X |
| language | English |
| last_indexed | 2024-04-24T07:58:38Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
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| series | Journal of Orthopaedic Translation |
| spelling | doaj.art-cd08d340fbd546ed986c17ae2840ad9b2024-04-18T04:20:26ZengElsevierJournal of Orthopaedic Translation2214-031X2024-03-0145197210Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidenceGuoju Hong0Shuqiang Li1Guanqiang Zheng2Xiaoxia Zheng3Qunzhang Zhan4Lin Zhou5Qiushi Wei6Wei He7Zhenqiu Chen8Traumatology & Orthopaedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR China; Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR ChinaDepartment of Oncology, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR ChinaDepartment of Rehabilitation, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR ChinaThe Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, PR ChinaThe Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, PR ChinaDepartment of Endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510700, PR China; Corresponding author. Department of Endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510700, PR China.Traumatology & Orthopaedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR China; Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR China; Corresponding author. Traumatology & Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR China.Traumatology & Orthopaedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR China; Department of Orthopaedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR China; Corresponding author. Traumatology & Orthopedics Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510378, PR China.Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, PR China; Corresponding author. Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, PR China.Background/objective: As the pivotal cellular mediators of bone resorption and pathological bone remodeling, osteoclasts have emerged as a prominent target for anti-resorptive interventions. Pinocembrin (PIN), a predominant flavonoid found in damiana, honey, fingerroot, and propolis, has been recognized for its potential therapeutic effects in osteolysis. The purpose of our project is to investigate the potential of PIN to prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms. Methods: The study commenced by employing protein-ligand molecular docking to ascertain the specific interaction between PIN and nuclear factor-κB (NF-κB) ligand (RANKL). Subsequently, PIN was introduced to bone marrow macrophages (BMMs) under the stimulation of RANKL. The impact of PIN on osteoclastic activity was assessed through the utilization of a positive TRAcP staining kit and a hydroxyapatite resorption assay. Furthermore, the study investigated the generation of reactive oxygen species (ROS) in osteoclasts induced by RANKL using H2DCFDA. To delve deeper into the underlying mechanisms, molecular cascades triggered by RANKL, including NF-κB, ROS, calcium oscillations, and NFATc1-mediated signaling pathways, were explored using Luciferase gene report, western blot analysis, and quantitative real-time polymerase chain reaction. Moreover, an estrogen-deficient osteoporosis murine model was established to evaluate the therapeutic effects of PIN in vivo. Results: In this study, we elucidated the profound inhibitory effects of PIN on osteoclastogenesis and bone resorption, achieved through repression of NF-κB and NFATc1-mediated signaling pathways. Notably, PIN also exhibited potent anti-oxidative properties by mitigating RANKL-induced ROS generation and augmenting activities of ROS-scavenging enzymes, ultimately leading to a reduction in intracellular ROS levels. Moreover, PIN effectively abrogated the expression of osteoclast-specific marker genes (Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-fos, and Mmp9), further underscoring its inhibitory impact on osteoclast differentiation and function. Additionally, employing an in vivo mouse model, we demonstrated that PIN effectively prevented osteoclast-induced bone loss resultant from estrogen deficiency. Conclusion: Our findings highlight the potent inhibitory effects of PIN on osteoclastogenesis, bone resorption, and RANKL-induced signaling pathways, thereby establishing PIN as a promising therapeutic candidate for the prevention and management of osteolytic bone diseases. The translational potential of this article: PIN serves as a promising therapeutic agent for the prevention and management of osteolytic bone diseases and holds promise for future clinical applications in addressing conditions characterized by excessive bone resorption. PIN is a natural compound found in various sources, including damiana, honey, fingerroot, and propolis. Its widespread availability and potential for therapeutic use make it an attractive candidate for further investigation and development as a clinical intervention.http://www.sciencedirect.com/science/article/pii/S2214031X24000032OsteoclastOsteolysisPinocembrinRANKLReactive oxygen species |
| spellingShingle | Guoju Hong Shuqiang Li Guanqiang Zheng Xiaoxia Zheng Qunzhang Zhan Lin Zhou Qiushi Wei Wei He Zhenqiu Chen Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence Journal of Orthopaedic Translation Osteoclast Osteolysis Pinocembrin RANKL Reactive oxygen species |
| title | Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence |
| title_full | Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence |
| title_fullStr | Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence |
| title_full_unstemmed | Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence |
| title_short | Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence |
| title_sort | therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease in vitro and in vivo evidence |
| topic | Osteoclast Osteolysis Pinocembrin RANKL Reactive oxygen species |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X24000032 |
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