Relevance of osteoclast-specific enzyme activities in cell-based in vitro resorption assays

Bernhardt, Anne; Koperski, K; Schumacher, Matthias; Gelinsky, Michael

doi:10.22203/ecm.v033a03

Cited by 42 publications

(27 citation statements)

References 19 publications

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“…Cathepsin K participates in osteoclast induced degradation of the sub-osteoclastic collagenous bone matrix [60][61][62]. The osteoclast enzyme TRAP is a substrate for cathepsin K and has been used as a molecular marker for osteoclasts [61,63]. Therefore, the inhibition of osteoclast formation may be a key mechanism for osteoporosis therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Effect of Nano-Montmorillonite on Osteoblast Differentiation, Mineral Density, and Osteoclast Differentiation in Bone Formation

Kim

Lee

et al. 2020

Nanomaterials

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Calcium-type montmorillonite, a phyllosilicate mineral, has diverse health benefits when introduced into the gastrointestinal tract or applied to the skin. However, the predominant use of this layered material has thus far been in traditional industries, despite its potential application in the pharmaceutical industry. We investigated the effects and mechanism of nano-montmorillonite (NM) on osteoblast and osteoclast differentiation in vivo and in vitro. We examined the osteogenic effects of NM with high calcium content (3.66 wt%) on alkaline phosphatase (ALP) activity, mineralization, bone microarchitecture, and expression level of osteoblast and osteoclast related genes in Ca-deficient ovariectomized (OVX) rats. Micro-computed tomography of OVX rats revealed that NM attenuated the low-Ca-associated changes in trabecular and cortical bone mineral density. It improved ALP activity and mineralization, as well as the expression of osteoblast and osteoclast differentiation associated genes. NM also activated the expression of runt-related transcription factor 2, osteocalcin, bone morphogenetic protein 2, and type 1 collagen via phosphorylated small mothers against decapentaplegic homolog 1/5/8 signaling. Further, NM repressed the expression of receptor activator for cathepsin K, nuclear factor kappa-B ligand and tartrate-resistant acid phosphatase. Therefore, NM inhibits osteoclastogenesis, stimulates osteoblastogenesis, and alleviates osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Effect of Nano-Montmorillonite on Osteoblast Differentiation, Mineral Density, and Osteoclast Differentiation in Bone Formation

Kim

Lee

et al. 2020

Nanomaterials

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“…Cement discs (6 mm diameter, 1 mm height, sterilized by γ-irradiation and pre-incubated in 1 ml of α-MEM containing 10% heat-inactivated FCS overnight) were seeded with PBMC containing 2*10 5 monocytes per sample. For indirect cultivation with cements extracts, PBMC containing 4*10 5 monocytes were seeded on dentin discs of 0.8 mm thickness, which have been cut from canine teeth of minipigs [ 17 ] in 48-well tissue culture polystyrene (TCPS) plates. Furthermore, 48-well TCPS plates were seeded with PBMC containing 1*10 5 monocytes.…”

Section: Methodsmentioning

confidence: 99%

“…Cell-based in vitro resorption assays are an important tool to simulate the in vivo biodegradation of resorbable bone graft materials to estimate their clinical performance [ 16 ]. In a recently published paper we analyzed the significance of osteoclast specific enzyme activities tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (CAII) and cathepsin K (CTSK) for the evaluation of resorption [ 17 ]. The central finding was that the correlation between osteoclast-related enzyme activities and resorption is dependent on the resorbed material.…”

Section: Introductionmentioning

confidence: 99%

“…The central finding was that the correlation between osteoclast-related enzyme activities and resorption is dependent on the resorbed material. It was postulated, that resorption of inorganic calcium phosphate materials is reflected by the intracellular TRAP and CAII activity, while in the case of collagen containing materials like dentin and mineralized collagen the extracellular TRAP and CTSK activity correlates to the resorbed area [ 17 ]. Brushite forming calcium phosphate bone cements display a rough surface [ 7 ] and therefore the discrimination between resorption pits and structural irregularities is not possible both on the non-modified brushite cement and the metal ion doped modifications.…”

Section: Introductionmentioning

confidence: 99%

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Osteoclastic differentiation and resorption is modulated by bioactive metal ions Co2+, Cu2+ and Cr3+ incorporated into calcium phosphate bone cements

et al. 2017

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Biologically active metal ions in low doses have the potential to accelerate bone defect healing. For successful remodelling the interaction of bone graft materials with both bone-forming osteoblasts and bone resorbing osteoclasts is crucial. In the present study brushite forming calcium phosphate cements (CPC) were doped with Co2+, Cu2+ and Cr3+ and the influence of these materials on osteoclast differentiation and activity was examined. Human osteoclasts were differentiated from human peripheral blood mononuclear cells (PBMC) both on the surface and in indirect contact to the materials on dentin discs. Release of calcium, phosphate and bioactive metal ions was determined using ICP-MS both in the presence and absence of the cells. While Co2+ and Cu2+ showed a burst release, Cr3+ was released steadily at very low concentrations (below 1 μM) and both calcium and phosphate release of the cements was considerably changed in the Cr3+ modified samples. Direct cultivation of PBMC/osteoclasts on Co2+ cements showed lower attached cell number compared to the reference but high activity of osteoclast specific enzymes tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (CAII) and cathepsin K (CTSK) and significantly increased gene expression of vitronectin receptor. Indirect cultivation with diluted Co2+ cement extracts revealed highest resorbed area compared to all other modifications and the reference. Cu2+ cements had cytotoxic effect on PBMC/osteoclasts during direct cultivation, while indirect cultivation with diluted extracts from Cu2+ cements did not provoke cytotoxic effects but a strictly inhibited resorption. Cr3+ doped cements did not show cytotoxic effects at all. Gene expression and enzyme activity of CTSK was significantly increased in direct culture. Indirect cultivation with Cr3+ doped cements revealed significantly higher resorbed area compared to the reference. In conclusion Cr3+ doped calcium phosphate cements are an innovative cement modification because of their high cytocompatibility and support of active resorption by osteoclasts.

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“…The initial injury to the tissue surrounding a bone implant induces an inflammatory response mediated by the cells of innate immunity, such as neutrophils, macrophages, and DCs. The cells, which are stuck to the implant walls, release reactive radicals, enzymes, and chemokines, which cause a cascade of inflammatory responses [4,5]. The mobilization of functional activity of innate immunity cells is directed by chemokines, cytokines, and integrins.…”

Section: Introductionmentioning

confidence: 99%

The Role of Dendritic Cells in Bone Loss and Repair

Плехова¹,

Lyapun²,

Gnedenkov³

et al. 2018

Dendritic Cells

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The cells of innate immunity, such as neutrophils, macrophages, and dendritic cells (DCs), stuck to the bone implant walls release reactive radicals, enzymes, and chemokines, which induced subsequent bone loss. DCs do not play a big role in bone homeostasis in steady-state conditions, but could act as osteoclasts precursors in inflammation foci of bone. The potent antigen-presenting cells responsible for activation of native T cells and modulation of T cell activity through RANK/RANKL pathway and other cytokines associated with osteoclastogenesis determine critically situated at the osteoimmune interface. The titanium (Ti) and magnesium (Mg), the metallic candidate in implant, including calcium-phosphate coating formation on them by method plasma electrolytic oxidation were used to evaluate the immune-modulatory effects of DCs. The calcium-phosphate coating on metals induced mature DC (mDC) phenotype, while Ti and Mg promoted a noninflammatory environment by supporting an immature DC (iDC) phenotype based on surface marker expression, cytokine production profiles, and cell morphology. These findings have numerous therapeutic implications in addition to DC's important role in regulating innate and adaptive immunity. A direct contribution of these cells to inflammation-induced bone loss establishes DC as a promising therapeutic target, not only for controlling inflammation but also for modulating bone destruction.

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Relevance of osteoclast-specific enzyme activities in cell-based in vitro resorption assays

Cited by 42 publications

References 19 publications

Effect of Nano-Montmorillonite on Osteoblast Differentiation, Mineral Density, and Osteoclast Differentiation in Bone Formation

Effect of Nano-Montmorillonite on Osteoblast Differentiation, Mineral Density, and Osteoclast Differentiation in Bone Formation

Osteoclastic differentiation and resorption is modulated by bioactive metal ions Co2+, Cu2+ and Cr3+ incorporated into calcium phosphate bone cements

The Role of Dendritic Cells in Bone Loss and Repair

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