iScience
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2025
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IF 4.1
Pan Liu,Jiezhong Deng,Yusheng Yang,Wenxi Bai,Shengtao Dong,Zehua Zhang
Tuberculosis (TB), caused by Mycobacterium tuberculosis ( M.tb ), is one of the most ancient diseases recorded. In cases of bone TB, it significantly disrupts bone homeostasis, though the precise mechanisms are poorly understood and effective treatment targets are scarce. Our study investigated the role of Rv1509 in the pathogenesis of bone TB. We found that Rv1509 enhances the differentiation of bone marrow macrophages (BMMs) into osteoclasts by activating the TLR2 pathway, which stimulates the production of IL-6 and TNF-α. This, in turn, indirectly inhibits osteoblast differentiation and mineralization. Additionally, Rv1509 directly impairs osteoblast function and enhances the secretion of RANKL via TLR2 signaling, creating a detrimental RANKL/OPG imbalance that promotes osteoclast differentiation and bone degradation. Notably, the injection of Rv1509 into mouse skulls led to extensive bone damage, highlighting its significant role as a virulence factor in the pathogenesis of bone TB.
研究领域:
免疫学
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微生物学
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骨骼生物学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2025
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IF 8.1
Liang Min-Hao,Zhou Lei,Li Juan,Liang Bin,Zhou Liang-Yun,Xue Feng-Feng,Jiang Li-Bo,Hong Wei
Postmenopausal osteoporosis (PMOP) is a predominant form of clinical osteoporosis. It has led to significant health and social burdens for older patients. Reestablishing the balance between osteogenic and osteoclastic is a crucial strategy for treating PMOP. Curcumin (Cur), a naturally derived polyphenolic substance, has gained recognition as a viable option for treating osteoporosis. Despite its potential, the clinical use of Cur is hindered by its limited bioavailability and the presence of side effects. Nanoparticles modified with aspartic acid octapeptide (ASP8) exhibit a strong affinity for bone tissue, facilitating targeted delivery. This study presents novel acid-responsive zeolite imidazolate framework-8 (ZIF) nanoparticles modified with ASP8 and loaded with Cur (Cur@ZIF@ASP8, CZA). Upon delivery by this nanoparticle drug delivery system, Cur can effectively regulate bone homeostasis, offering a potential therapeutic strategy for osteoporosis. This study demonstrated that CZA nanoparticles could successfully transport Cur to bone tissue without significant toxicity. Furthermore, nanoparticles promote bone formation and inhibit osteoclast activity. They also modify the expression of related genes and proteins, such as OCN, ALP, CTSK, and MMP9. Significant evaluations utilizing microcomputed tomography, Masson’s staining, hematoxylin and eosin staining, and immunofluorescence staining demonstrated that intravenous CZA administration in ovariectomized mice resulted in bone destruction while simultaneously reducing overall bone loss. In conclusion, CZA nanoparticles hold promise as a therapeutic option for osteoporosis.
研究领域:
医学
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材料科学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2018
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IF 4.432
Tingting Shen,Weihu Yang,Xinkun Shen,Weizhen Chen,Bailong Tao,Xiaoqing Yang,Jianping Yuan,Peng Liu,Kaiyong Cai
Maintaining the balance between bone formation and bone resorption as well as reducing bacterial infection are two major challenges for titanium (Ti) when it is used as the implant in orthopedic surgery. Because of its excellent properties, including anti-inflammatory, antimicrobial, promoting osteoblasts, and inhibiting osteoclasts growth, lactoferrin (LF) is a potential bioactive molecule for surface modification of Ti implants. Inspired by the highly hierarchical structure of natural bone tissue, in this work, a polydopamine-assisted hydroxyapatite and lactoferrin multilayer structure (PDA-HA-LF) was prepared onto the Ti substrate surface by a biomimetic approach and spin-assisted layer-by-layer (LBL) assembly technique. Meanwhile, its capabilities on regulation of bone balance and antibacterial properties were measured with cell experiments and antimicrobial activity in vitro. Furthermore, the regulation theory was investigated by qPCR and theoretical simulation. The results showed that the biological properties of LF are highly correlated with its concentration. High concentration of LF was toxic to osteoblasts but has obvious effects on inhibition of osteoclasts and bacteria (S. aureus and E. coli). However, through polydopamine-assisted hydroxyapatite deposition, cytotoxicity of LF could be improved. The modified Ti implant could greatly improve the proliferation and differentiation of osteoblasts. Meanwhile, the activity of osteoclasts was somewhat inhibited, which indicated that the modified Ti implant could efficiently regulate the balance between bone resorption and bone formation, as well as have a certain antibacterial effect.
研究领域:
材料科学
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生物材料
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组织工程
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骨科
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
·
2024
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IF 4.8
Jiaxin Zhang,Jiaqi Chen,Hui Wang,Chang Liu,Xin Yin,Haotian Bai,Mingwei Xu,Zuhao Li,Yanbing Wang,Xiujie Zhu,Xiaonan Wang,Ming Ren,Haowen Xue,Jincheng Wang,He Liu,Xin Zhao
Osteogenic–osteoclastic microenvironment imbalance impairs osseointegration between joint prostheses and the marrow cavity, which is a crucial contributor to the high incidence of complications such as implant loosening and periprosthetic fractures in osteoporosis (OPs). Previously, we employed hydrogel-based bisphosphonate (BPs) coatings on 3D-printed porous titanium alloy implants (pTi) to modulate the OPs microenvironment through controlled release. However, challenges persisted, including the limited duration of BPs release and associated organic material degradation-induced toxicity. To address these issues, we modified pTi surfaces by introducing chemically stable zeolites and BPs. In this study, we applied Ca 2+ -functionalized hierarchical zeolite coating on pTi for the first time. By combining mesoporous adsorption and Ca 2+ chelation, we achieved efficient encapsulation of zoledronate (ZOL), creating a bioactive interface characterized by a spatial gradient structure with a “microporous-mesoporous-macroporous” morphology. The coating achieves the release of ZOL through the mesoporous structure and facilitates the gradual release of chelated ZOL via ion exchange, resulting in hierarchical drug delivery. Moreover, the spatial gradient structure of the coatings significantly influenced cell extension. Simultaneously, we constructed a bioactive coating with a drug concentration gradient, achieving graded drug release within the microenvironment, which facilitated the accurate regulation of osteogenesis and bone resorption. This coating has the potential to substantially enhance the management of postoperative complications in OPs patients undergoing prosthetic replacement surgery by achieving a balanced osteogenic-osteoclastic response.
研究领域:
材料科学
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生物医学工程
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骨科
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药剂学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）