Role of the RANK/RANKL/OPG and Wnt/β-Catenin Systems in CKD Bone and Cardiovascular Disorders

Carrillo-López, Natalia; Martínez-Arias, Laura; Fernández-Villabrille, Sara; Ruiz-Torres, María Piedad; Dusso, Adriana; Cannata‐Andía, Jorge B.; Naves-Díaz, Manuel; Panizo, Sara

doi:10.1007/s00223-020-00803-2

Cited by 56 publications

(52 citation statements)

References 157 publications

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“…38 Also fibroblast growth factor 23 increases early in CKD and exerts inhibitory action on the Wnt/β-catenin pathway by activation of Dickkopf1 through interaction with soluble Klotho. 39,40 J o u r n a l P r e -p r o o f…”

Section: Repressed Wnt/β-catenin Signallingmentioning

confidence: 99%

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

Haarhaus

Evenepoel

2021

Kidney International

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Section: Repressed Wnt/β-catenin Signallingmentioning

confidence: 99%

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

Haarhaus

Evenepoel

2021

Kidney International

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“…BMSCs participate in bone resorption by secreting OPG/RANKL to regulate preosteoclast differentiation and activation. [ 47 ] The phenomenon of osteoclast inhibition in vivo may be due to the paracrine effect of autophagy‐regulated BMSCs to influence the osteoclastogenesis from the appropriate hematopoietic lineage cells. In addition, it is also possible that the sustained‐release rapamycin from the 3D printed bioactive prosthetic interfaces directly acts on osteoclasts, which is worthy of further exploration.…”

Section: Resultsmentioning

confidence: 99%

Engineering Multifunctional Hydrogel‐Integrated 3D Printed Bioactive Prosthetic Interfaces for Osteoporotic Osseointegration

Zhao

Wang

et al. 2022

Adv Healthcare Materials

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3D printed porous titanium alloy implants is an advanced orthopedic material for joint replacement. However, the high risk of aseptic loosening and periprosthetic infection is difficult to avoid, and the declined autophagy of osteoporosis‐derived bone marrow mesenchymal stem cells (OP‐BMSCs) further severely impairs the osseointegration under the osteoporotic circumstance. It is thus becoming urgently significant to develop orthopedic materials with autophagy regulation and antibacterial bioactivity. In this regard, a novel class of multifunctional hydrogel‐integrated 3D printed bioactive prosthetic interfaces is engineered for in situ osseointegration in osteoporosis. The hydrogel is fabricated from the dynamic crosslinking of synthetic polymers, natural polymers, and silver nanowires to deliver autophagy‐regulated rapamycin. Therefore, the resultant soft material exhibits antibacterial ability, biocompatibility, degradability, conductive, self‐healing, and stimuli‐responsive abilities. In vitro experiments demonstrate that the hydrogel‐integrated 3D printed bioactive prosthetic interfaces can restore the declined cellular activities of OP‐BMSCs by upregulating the autophagy level and show excellent antibacterial activity against S. aureus and MRSA. More remarkably, the multifunctional 3D printed bioactive prosthetic interfaces significantly improve osseointegration and inhibit infection in osteoporotic environment in vivo. This study provides an efficient strategy to develop novel prosthetic interfaces to reduce complications after arthroplasty for patients with osteoporosis.

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“…For transwell co-cultures, profound changes in gene expression, with a strong and significant decrease of OPG in PPFs of both origins (hundredfold in orthopaedic/twentyfold decrease in dental co-cultures) were The RANKL/OPG ratios, which were rather low in monolayer co-cultures of both origins, were found to be significantly higher in transwell cultures and reached similar levels to original periprosthetic tissues. Several reviews state the importance of the RANKL/ OPG pathway for the bone homeostasis, low levels of OPG lead to an activation of the osteoclastogenesis favoring bone resorption (41,42). Elevated RANKL/OPG ratio were also found in peri-mucositis triggered by bacteria, peri-implantitis and gingival crevicular fluid of diseased peri-implant tissues (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation

et al. 2022

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ObjectivesEndoprosthetic loosening still plays a major role in orthopaedic and dental surgery and includes various cellular immune processes within peri-implant tissues. Although the dental and orthopaedic processes vary in certain parts, the clinical question arises whether there are common immune regulators of implant loosening. Analyzing the key gene expressions common to both processes reveals the mechanisms of osteoclastogenesis within periprosthetic tissues of orthopaedic and dental origin.MethodsDonor peripheral blood mononuclear cells (PBMCs) and intraoperatively obtained periprosthetic fibroblast-like cells (PPFs) were (co-)cultured with [± macrophage-colony stimulating factor (MCSF) and Receptor Activator of NF-κB ligand (RANKL)] in transwell and monolayer culture systems and examined for osteoclastogenic regulations [MCSF, RANKL, osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα)] as well as the ability of bone resorption. Sequencing analysis compared dental and orthopaedic (co-)cultures.ResultsMonolayer co-cultures of both origins expressed high levels of OPG, resulting in inhibition of osteolysis shown by resorption assay on dentin. The high OPG-expression, low RANKL/OPG ratios and a resulting inhibition of osteolysis were displayed by dental and orthopaedic PPFs in monolayer even in the presence of MCSF and RANKL, acting as osteoprotective and immunoregulatory cells. The osteoprotective function was only observed in monolayer cultures of dental and orthopaedic periprosthetic cells and downregulated in the transwell system. In transwell co-cultures of PBMCs/PPFs profound changes of gene expression, with a significant decrease of OPG (20-fold dental versus 100 fold orthopaedic), were identified. Within transwell cultures, which offer more in vivo like conditions, RANKL/OPG ratios displayed similar high levels to the original periprosthetic tissue. For dental and orthopaedic implant loosening, overlapping findings in principal component and heatmap analysis were identified.ConclusionsThus, periprosthetic osteoclastogenesis may be a correlating immune process in orthopaedic and dental implant failure leading to comparable reactions with regard to osteoclast formation. The transwell cultures system may provide an in vivo like model for the exploration of orthopaedic and dental implant loosening.

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Role of the RANK/RANKL/OPG and Wnt/β-Catenin Systems in CKD Bone and Cardiovascular Disorders

Cited by 56 publications

References 157 publications

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

Engineering Multifunctional Hydrogel‐Integrated 3D Printed Bioactive Prosthetic Interfaces for Osteoporotic Osseointegration

Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation

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