Contribution of Type H Blood Vessels to Pathologic Osteogenesis and Inflammation in an Experimental Spondyloarthritis Model

Kaaij, Merlijn H.; Hamburg, Jan Piet van; Grüneboom, Anika; Kan, Yik Y.; Pots, Desirée; Schett, Georg; Ruijven, L.J. van; Duivenvoorde, Leonie M. van; Huitema, Leonie F. A.; Baeten, Dominique; Tas, Sander W.

doi:10.1002/art.42449

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…3b). This cell subset was also present in the diaphysis of long bones (Kusumbe et al 2014) and vertebrae (Kaaij et al 2023), but little is known about their functions currently, which can be a future issue to explore.…”

Section: Discussionmentioning

confidence: 99%

Occlusal Force Maintains Alveolar Bone Homeostasis via Type H Angiogenesis

Chen,

Yin,

Luo

et al. 2023

J Dent Res

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Physiologically, teeth and periodontal tissues are exposed to occlusal forces throughout their lifetime. Following occlusal unloading, unbalanced bone remodeling manifests as a net alveolar bone (AB) loss. This phenomenon is termed alveolar bone disuse osteoporosis (ABDO), the underlying mechanism of which remains unclear. Type H vessels, a novel capillary subtype tightly coupled with osteogenesis, reportedly have a role in skeletal remodeling; however, their role in ABDO is not well studied. In the present study, we aimed to explore the pathogenesis of and therapies for ABDO. The study revealed that type H endothelium highly positive for CD31 and endomucin was identified in the periodontal ligament (PDL) but rarely in the AB of the mice. In hypofunctional PDL, the density of type H vasculature and coupled osterix+ (OSX+) osteoprogenitors declined significantly. In addition, the angiogenic factor Slit guidance ligand 3 (SLIT3) was downregulated in the disused PDL, and periodontal injection of the recombinant SLIT3 protein partially ameliorated type H vessel dysfunction and AB loss in ABDO mice. With regard to the molecular mechanism, a mechanosensory signaling circuit, PIEZO1/Ca2+/HIF-1α/SLIT3, was validated by applying cyclic compression to 3-dimensional–cultured PDL cells using the Flexcell FX-5000 compression system. In summary, PDL plays a pivotal role in mechanotransduction by translating physical forces into the intracellular signaling axis PIEZO1/Ca2+/HIF-1α/SLIT3, which promotes type H angiogenesis and OSX+ cell–related osteogenensis, thereby contributing to AB homeostasis. Our findings advance the understanding of PDL in AB disorders. Further therapies targeting SLIT3 may provide new insights into preventing bone loss in ABDO.

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Section: Discussionmentioning

confidence: 99%

Occlusal Force Maintains Alveolar Bone Homeostasis via Type H Angiogenesis

Chen,

Yin,

Luo

et al. 2023

J Dent Res

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Advanced application of carbohydrate-based micro/nanoparticles for rheumatoid arthritis

Cui,

Pi,

Qin

et al. 2024

International Journal of Biological Macromolecules

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Targeting strategies for bone diseases: signaling pathways and clinical studies

Wang

Liu

et al. 2023

Sig Transduct Target Ther

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Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting strategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of the classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key membrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug delivery, different delivery strategies targeting bone matrix, bone marrow, and specific bone cells are summarized with a comparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area.

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Contribution of Type H Blood Vessels to Pathologic Osteogenesis and Inflammation in an Experimental Spondyloarthritis Model

Cited by 3 publications

References 58 publications

Occlusal Force Maintains Alveolar Bone Homeostasis via Type H Angiogenesis

Occlusal Force Maintains Alveolar Bone Homeostasis via Type H Angiogenesis

Advanced application of carbohydrate-based micro/nanoparticles for rheumatoid arthritis

Targeting strategies for bone diseases: signaling pathways and clinical studies

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