Treatment with anti‐Sclerostin antibody to stimulate mandibular bone formation

Tamplen, Matthew; Fowler, Tristan W.; Markey, Jeffery; Knott, P. Daniel; Suva, Larry J.; Alliston, Tamara

doi:10.1002/hed.25128

Cited by 13 publications

(17 citation statements)

References 39 publications

(112 reference statements)

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“…Sclerostin (SOST) is produced by osteocytes and has anti-anabolic effects on bone formation; inhibition of SOST can stimulate bone formation [81]. The SOST secretion was significantly reduced after 7 days in the RPM samples, as compared to the 1 g controls.…”

Section: Discussionmentioning

confidence: 99%

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Mann

Grimm

Corydon

et al. 2019

IJMS

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Human cells, when exposed to both real and simulated microgravity (s-µg), form 3D tissue constructs mirroring in vivo architectures (e.g., cartilage, intima constructs, cancer spheroids and others). In this study, we exposed human foetal osteoblast (hFOB 1.19) cells to a Random Positioning Machine (RPM) for 7 days and 14 days, with the purpose of investigating the effects of s-µg on biological processes and to engineer 3D bone constructs. RPM exposure of the hFOB 1.19 cells induces alterations in the cytoskeleton, cell adhesion, extra cellular matrix (ECM) and the 3D multicellular spheroid (MCS) formation. In addition, after 7 days, it influences the morphological appearance of these cells, as it forces adherent cells to detach from the surface and assemble into 3D structures. The RPM-exposed hFOB 1.19 cells exhibited a differential gene expression of the following genes: transforming growth factor beta 1 (TGFB1, bone morphogenic protein 2 (BMP2), SRY-Box 9 (SOX9), actin beta (ACTB), beta tubulin (TUBB), vimentin (VIM), laminin subunit alpha 1 (LAMA1), collagen type 1 alpha 1 (COL1A1), phosphoprotein 1 (SPP1) and fibronectin 1 (FN1). RPM exposure also induced a significantly altered release of the cytokines and bone biomarkers sclerostin (SOST), osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN), interleukin 1 beta (IL-1β) and tumour necrosis factor 1 alpha (TNF-1α). After the two-week RPM exposure, the spheroids presented a bone-specific morphology. In conclusion, culturing cells in s-µg under gravitational unloading represents a novel technology for tissue-engineering of bone constructs and it can be used for investigating the mechanisms behind spaceflight-related bone loss as well as bone diseases such as osteonecrosis or bone injuries.

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Section: Discussionmentioning

confidence: 99%

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Mann

Grimm

Corydon

et al. 2019

IJMS

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“…While this study used an MMP-sensitive PEG hydrogel, other hydrogels that support osteocyte differentiation could readily be infilled into the stiff 3D-printed structure and attain nearphysiological levels of strain in the bone-like layer. Other environmental considerations that are known to influence osteocytes could be studied within this model, which include pH, [89] oxygen tension, [90] drug treatment, [91] hormone levels, [92,93] or inflammatory mediators. [94] Further, this unique model may generate new insights into the osteocyte's role in propagating osteoarthritis progression in response to the changes in fluid flow.…”

Section: Doi: 101002/adhm202001226mentioning

confidence: 99%

A 3D, Dynamically Loaded Hydrogel Model of the Osteochondral Unit to Study Osteocyte Mechanobiology

Wilmoth

Ferguson

Bryant

2020

Adv Healthcare Materials

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Osteocytes are mechanosensitive cells that orchestrate signaling in bone and cartilage across the osteochondral unit. The mechanisms by which osteocytes regulate osteochondral homeostasis and degeneration in response to mechanical cues remain unclear. This study introduces a novel 3D hydrogel bilayer composite designed to support osteocyte differentiation and bone matrix deposition in a bone-like layer and to recapitulate key aspects of the osteochondral unit's complex loading environment. The bilayer hydrogel is fabricated with a soft cartilage-like layer overlaying a stiff bone-like layer. The bone-like layer contains a stiff 3D-printed hydrogel structure infilled with a soft, degradable, cellular hydrogel. The IDG-SW3 cells embedded within the soft hydrogel mature into osteocytes and produce a mineralized collagen matrix. Under dynamic compressive strains, near-physiological levels of strain are achieved in the bone layer (≤ 0.08%), while the cartilage layer bears the majority of the strains (>99%). Under loading, the model induces an osteocyte response, measured by prostaglandin E2, that is frequency, but not strain, dependent: a finding attributed to altered fluid flow within the composite. Overall, this new hydrogel platform provides a novel approach to study osteocyte mechanobiology in vitro in an osteochondral tissue-mimetic environment. Osteocytes are mechanosensitive cells that help to orchestrate signaling in bone and cartilage across the osteochondral unit. Yet the mechanisms by which osteocytes regulate osteochondral

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“…Regarding periodontal tissues, available data suggest that the efficacy of local administration of sclerostin antibodies remains questionable due to heterogeneous results (Han et al, 2015;Taut et al, 2013). Systemic administration of these agents has showed significant effects on the periodontium, increasing the height of alveolar crest and reducing the distance from CEJ to the alveolar bone crest Tamplen et al, 2018). Furthermore, systemic administration of these antibodies also showed positive effects in animal models of periodontitis, with an increase in bone-mineral apposition rate, bone density, bone-volume fraction, trabecular number and thickness, with a reversion of bone loss due to periodontitis and a reduced CEJ-alveolar crest distance (Chen et al, 2015;Taut et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, a local injection of antisclerostin in gingival tissues showed a limited effect on bone healing. Liu et al (2018) and Tamplen et al (2018) evaluated the effects of antisclerostin on the alveolar crest of rats. Both studies found that the systemic administration of the antibody increased the alveolar crest, identified as the reduction of the distance from the CEJ to the top of the alveolar bone crest.…”

Section: Sclerostin and Dkk-1 Antibodiesmentioning

confidence: 99%

The role of bone anabolic drugs in the management of periodontitis: a scoping review

Cecoro¹,

Paoletta²,

Annunziata³

et al. 2021

eCM

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The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.

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Treatment with anti‐Sclerostin antibody to stimulate mandibular bone formation

Abstract: Treatment with anti-Scl-Ab significantly increased mandibular bone mass and alveolar height in wild type mice and normalized mandibular bone mass and alveolar height in Ts65Dn mice. The anti-Scl-Ab therapy represents a novel method for increasing mandibular bone formation.

Cited by 13 publications

References 39 publications

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

A 3D, Dynamically Loaded Hydrogel Model of the Osteochondral Unit to Study Osteocyte Mechanobiology

The role of bone anabolic drugs in the management of periodontitis: a scoping review

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