Chao Ma

All Publications

• Cycloastragenol prevents bone loss via inhibiting osteoclast activity in glucocorticoid-induced osteonecrosis of the femoral head: Anin vivostudy. Journal of orthopaedic translation Wang, G., Ma, C., Mo, L., Chen, J., Yuan, J., Xu, J., He, W. 2024; 45: 178-187

  Abstract

  Background: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common bone and joint disease. There is currently a lack of effective treatment for GIONFH, and the disease progression may lead to total hip arthroplasty (THA). The exact mechanism of GIONFH pathogenesis remains unsettled, and emerging evidence indicates that the overactivation of osteoclasts plays a pivotal role in the occurrence and progression of this condition. Our previous study has shown that cycloastragenol (CAG), a triterpenoid saponin with multiple bioactivities, is a natural osteoclast inhibitor and has a protective effect on bone loss. However, its effect on GIONFH remains unclear.Methods: In this study, methylprednisolone (MPS) (20mg/kg) was administered via gluteal muscle injection to female Sprague-Dawley (SD) rats to induce GIONFH, and different doses of CAG (5 and 15mg/kg) were dispensed intraperitoneally for intervention. Micro-CT screening and angiography were applied to determine the shaping of necrotic lesions, the loss of trabecular bone, and the change in the local blood supply. The molecular mechanism was established by Real-time qPCR and Western blotting. Hematoxylin and eosin (H&E) staining was performed to identify empty lacunae in the femoral head.Results: CAG treatment shanked the necrotic lesion area, inhibited the trabecular bone loss, and improved the local blood supply in the femoral head. In addition, CAG medication lowered the ratio of Tnfsf11 (encoding RANKL) to Tnfrsf11b (encoding OPG) and the expression of osteoclast-specific genes, including Acp5 and Ctsk. Consistently, CAG treatment exhibited a dose-dependent weakening effect on the expression of osteoclastogenesis and bone resorption-related proteins, including TRAP, CTSK, and MMP9. CAG addition also alleviated the occurrence of empty lacunae in the subchondral region.Conclusion: Our discoveries demonstrate that CAG is a potential option for hip preservation therapy in GIONFH patients.Translational potential of this article: The protective effect of CAG on rats with GIONFH can be translated into clinical use.

  View details for DOI 10.1016/j.jot.2024.01.009

  View details for PubMedID 38549807

• Tanshinone I attenuates estrogen-deficiency bone loss via inhibiting RANKL-induced MAPK and NF-κB signaling pathways INTERNATIONAL IMMUNOPHARMACOLOGY Ma, C., Wang, Z., Mo, L., Wang, X., Zhou, G., Yi, C., Niu, W., Liu, Y. 2024; 127: 111322

  Abstract

  This study aims to reveal the role of Tanshinone I (TI) in inhibiting osteoclast activity and bone loss in vitro and in vivo, as well as elucidate its underlying molecular mechanism.A mouse model of estrogen deficiency was used to assess the inhibitory effect of TI on osteoclast activity and subsequent bone loss. To validate the impact of TI on osteoclast formation, TRAcP staining and pseudopodia belt staining were conducted. The expressions of osteoclast-specific genes and proteins were evaluated using RT-PCR and Western Blot analyses. Additionally, immunofluorescence staining was employed to examine the effect of TI on p65 nuclear translocation and the expression level of reactive oxygen species (ROS).TI demonstrated significant efficacy in alleviating bone mass loss and suppressing osteoclast activity and function in ovariectomized mice. This outcome was predominantly ascribed to a decrease in ROS levels, thereby impeding the NF-κB signaling pathway and the translocation of p65 to the nucleus. Additionally, TI hindered the RANKL-induced phosphorylation of the MAPK signaling pathway. Moreover, TI played a role in the reduction of osteoclast-specific genes and proteins.To summarize, this study sheds light on TI's capacity to modulate various signaling pathways triggered by RANKL, effectively impeding osteoclast formation and mitigating bone loss resulting from estrogen deficiency. Consequently, TI emerges as a promising therapeutic option for estrogen-deficiency bone loss.

  View details for DOI 10.1016/j.intimp.2023.111322

  View details for Web of Science ID 001135551000001

  View details for PubMedID 38064814

• Dihydrotanshinone I attenuates estrogen-deficiency bone loss through RANKL-stimulated NF-κB, ERK and NFATc1 signaling pathways. International immunopharmacology Ma, C., Mo, L., Wang, Z., Peng, D., Zhou, C., Niu, W., Liu, Y., Chen, Z. 2023; 123: 110572

  Abstract

  Postmenopausal osteoporosis, a chronic condition that predominantly affects postmenopausal women, presents a significant impediment to their overall well-being. The condition arises from estrogen deficiency, leading to enhanced osteoclast activity. Salvia miltiorrhiza, a well-established Chinese herbal medicine with a history of clinical use for osteoporosis treatment, contains diverse active constituents that have shown inhibitory effects on osteoclast formation and bone loss. Dihydrotanshinone I (DTI), a phenanthrenonequinone compound derived from the root of Salvia miltiorrhiza, has been identified as a potential therapeutic agent, although its mechanism of action on osteoclasts remains elusive. In this study, we aimed to elucidate the inhibitory potential of DTI on RANKL-induced osteoclastogenesis. We observed the ability of DTI to effectively impede the expression of key osteoclast-specific genes and proteins, as assessed by Real-time PCR and Western Blotting analyses. Mechanistically, DTI exerted its inhibitory effects on osteoclast formation by modulating critical signaling pathways including NF-κB, ERK, and calcium ion signaling. Notably, DTI intervention disrupted the nuclear translocation and subsequent transcriptional activity of the NFATc1, thus providing mechanistic insights into its inhibitory role in osteoclastogenesis. To further assess the therapeutic potential of DTI, we employed an ovariectomized osteoporosis animal model to examine its impact on bone loss. Encouragingly, DTI demonstrated efficacy in mitigating bone loss induced by estrogen deficiency. In conclusion, our investigation elucidates the ability of DTI to regulate multiple signaling pathways activated by RANKL, leading to the inhibition of osteoclast formation and prevention of estrogen-deficiency osteoporosis. Consequently, DTI emerges as a promising candidate for the treatment of osteoporosis.

  View details for DOI 10.1016/j.intimp.2023.110572

  View details for PubMedID 37572501

• Combination of Distinct Vascular Stem/Progenitor Cells for Neovascularization and Ischemic Rescue. Arteriosclerosis, thrombosis, and vascular biology Zhao, L., Lee, A. S., Sasagawa, K., Sokol, J., Wang, Y., Ransom, R. C., Zhao, X., Ma, C., Steininger, H. M., Koepke, L. S., Borrelli, M. R., Brewer, R. E., Lee, L. L., Huang, X., Ambrosi, T. H., Sinha, R., Hoover, M. Y., Seita, J., Weissman, I. L., Wu, J. C., Wan, D. C., Xiao, J., Longaker, M. T., Nguyen, P. K., Chan, C. K. 2023

  Abstract

  Peripheral vascular disease remains a leading cause of vascular morbidity and mortality worldwide despite advances in medical and surgical therapy. Besides traditional approaches, which can only restore blood flow to native arteries, an alternative approach is to enhance the growth of new vessels, thereby facilitating the physiological response to ischemia.The ActinCreER/R26VT2/GK3 Rainbow reporter mouse was used for unbiased in vivo survey of injury-responsive vasculogenic clonal formation. Prospective isolation and transplantation were used to determine vessel-forming capacity of different populations. Single-cell RNA-sequencing was used to characterize distinct vessel-forming populations and their interactions.Two populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells: VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105highSca1low, which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105lowSca1high and forms stunted vessels and fat. Interestingly, cotransplantation of VSPC1 and VSPC2 is required to form functional vessels that improve perfusion in the mouse hindlimb ischemia model. Similarly, VSPC1 and VSPC2 populations isolated from human adipose tissue could rescue the ischemic condition in mice.These findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.

  View details for DOI 10.1161/ATVBAHA.122.317943

  View details for PubMedID 37051932

• Integrated Bioinformatic Analysis of the Shared Molecular Mechanisms Between Osteoporosis and Atherosclerosis. Frontiers in endocrinology Mo, L., Ma, C., Wang, Z., Li, J., He, W., Niu, W., Chen, Z., Zhou, C., Liu, Y. 2022; 13: 950030

  Abstract

  Osteoporosis and atherosclerosis are common in the elderly population, conferring a heavy worldwide burden. Evidence links osteoporosis and atherosclerosis but the exact underlying common mechanism of its occurrence is unclear. The purpose of this study is to further explore the molecular mechanism between osteoporosis and atherosclerosis through integrated bioinformatic analysis.The microarray data of osteoporosis and atherosclerosis in the Gene Expression Omnibus (GEO) database were downloaded. The Weighted Gene Co-Expression Network Analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to identify the co-expression genes related to osteoporosis and atherosclerosis. In addition, the common gene targets of osteoporosis and atherosclerosis were analyzed and screened through three public databases (CTD, DISEASES, and GeneCards). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. Then, the common microRNAs (miRNAs) in osteoporosis and atherosclerosis were screened out from the Human microRNA Disease Database (HMDD) and the target genes of whom were predicted through the miRTarbase. Finally, the common miRNAs-genes network was constructed by Cytoscape software.The results of common genes analysis showed that immune and inflammatory response may be a common feature in the pathophysiology of osteoporosis and atherosclerosis. Six hub genes (namely, COL1A1, IBSP, CTSD, RAC2, MAF, and THBS1) were obtained via taking interaction of different analysis results. The miRNAs-genes network showed that has-let-7g might play an important role in the common mechanisms between osteoporosis and atherosclerosis.This study provides new sights into shared molecular mechanisms between osteoporosis and atherosclerosis. These common pathways and hub genes may offer promising clues for further experimental studies.

  View details for DOI 10.3389/fendo.2022.950030

  View details for PubMedID 35937806

  View details for PubMedCentralID PMC9353191