Measuring mineralised tissue formation and resorption in a human 3D osteoblast-osteoclast co-culture model

Remmers, Stefan; Mayer, Dana C.; Melke, J.; Ito, Keita; Hofmann, Sandra

doi:10.22203/ecm.v040a12

Cited by 15 publications

(42 citation statements)

References 38 publications

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“…This simulates a bone remodeling environment that is a step closer to the physiological process of bone remodeling versus only resorption, although in vivo the order is typically reversed: first, ECM is resorbed by OC, then new ECM is deposited by OB [ 46 ]. However, the process of creating a mineralized matrix may introduce a variation in substrate size even prior to initiating the co-culture [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Examples are 2-photon microscopy for thin samples and micro computed tomography (μCT) [ 49 ]. Due to the non-destructive nature of μCT, it is well suited to monitor mineralized volume change over time within the same samples over a longer period of time [ 47 , 49 , 50 ]. Registering consecutive images can even show both formation and resorption events within the same set of images of the same sample if both mineralizing OBs and resorbing OCs were present [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Due to the non-destructive nature of μCT, it is well suited to monitor mineralized volume change over time within the same samples over a longer period of time [ 47 , 49 , 50 ]. Registering consecutive images can even show both formation and resorption events within the same set of images of the same sample if both mineralizing OBs and resorbing OCs were present [ 47 ]. The usefulness of such a monitoring tool is however dependent on the envisaged resolution versus the corresponding potential cell-damage caused by radiation exposure [ 51 , 52 ], and requires the use of sterile scannable culture vessels, which poses some practical constraints.…”

Section: Discussionmentioning

confidence: 99%

“…ALP makes phosphates available to be incorporated into the matrix [ 57 ] and TRAP has been associated with migration and activation of OC [ 58 ]. Their presence is not conclusive proof that formation and resorption are occurring because ALP is expressed already in differentiating MSCs [ 59 ] and TRAP is expressed on monocytes as well [ 47 ]. Still, there is a correlation between their presence and that of OB and OC activity.…”

Section: Discussionmentioning

confidence: 99%

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Osteoblast-osteoclast co-cultures: A systematic review and map of available literature

et al. 2021

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Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the use of animal models. One approach to replace and reduce the use of animal models is to use in vitro cell-culture models. To study bone physiology, bone diseases and drugs, many studies have been published using osteoblast-osteoclast co-cultures. The use of osteoblast-osteoclast co-cultures is usually not clearly mentioned in the title and abstract, making it difficult to identify these studies without a systematic search and thorough review. As a result, researchers are all developing their own methods, leading to conceptually similar studies with many methodological differences and, as a consequence, incomparable results. The aim of this study was to systematically review existing osteoblast-osteoclast co-culture studies published up to 6 January 2020, and to give an overview of their methods, predetermined outcome measures (formation and resorption, and ALP and TRAP quantification as surrogate markers for formation and resorption, respectively), and other useful parameters for analysis. Information regarding these outcome measures was extracted and collected in a database, and each study was further evaluated on whether both the osteoblasts and osteoclasts were analyzed using relevant outcome measures. From these studies, additional details on methods, cells and culture conditions were extracted into a second database to allow searching on more characteristics. The two databases presented in this publication provide an unprecedented amount of information on cells, culture conditions and analytical techniques for using and studying osteoblast-osteoclast co-cultures. They allow researchers to identify publications relevant to their specific needs and allow easy validation and comparison with existing literature. Finally, we provide the information and tools necessary for others to use, manipulate and expand the databases for their needs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Osteoblast-osteoclast co-cultures: A systematic review and map of available literature

et al. 2021

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show abstract

“…This essentially simulates a bone remodeling environment that is a step closer to the physiological process of bone remodeling versus only resorption, although in vivo the order in which this typically happens is reversed: first, damaged ECM is resorbed by OC, then new ECM is deposited by OB (52). However, the process of creating a mineralized matrix may introduce a variation in substrate size even prior to initiating the co-culture (53). Also, many in vitro formation experiments, while being able to produce the ECM constituents collagen and mineral, are not (yet) producing real bone ECM (51).…”

Section: Resorptionmentioning

confidence: 99%

Osteoblast-osteoclast co-cultures: a systematic review and map of available literature

Remmers

Wildt

Vis

et al. 2021

Preprint

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Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the use of animal models. One approach to replace and reduce the use of animal models in research is using in vitro cell-culture models. To study bone physiology, bone diseases and drugs, many studies have been published using osteoblast-osteoclast co-cultures. The use of osteoblast-osteoclast co-cultures is usually not clearly mentioned in the title and abstract, making it difficult to identify these studies without a systematic search and thorough review. As a result, researchers are all developing their own methods from the ground up, leading to conceptually similar studies with many methodological differences and, as a direct consequence, incomparable results. The aim of this study was to systematically review existing osteoblast-osteoclast co-culture studies published up to 6 January 2020, and to give an overview of their methods, predetermined outcome measures (formation and resorption, and ALP and TRAP quantification as surrogate markers for formation and resorption, respectively), and other useful parameters for analysis. Information regarding these outcome measures was extracted and collected in a database, and each study was further evaluated on whether both the osteoblasts and osteoclasts were analyzed using relevant outcome measures. From these studies, additional details on methods, cells and culture conditions were extracted into a second database to allow searching on more characteristics. The two databases presented in this publication provide an unprecedented amount of information on cells, culture conditions and analytical techniques for using and studying osteoblast-osteoclast co-cultures. They allow researchers to identify publications relevant to their specific needs and allow easy validation and comparison with existing literature. Finally, we provide the information and tools necessary for others to use, manipulate and expand the databases for their needs.

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Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models

Wildt

Bartels

Sommerdijk

et al. 2022

Adv Funct Materials

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Human in vitro bone models can create the possibility for investigation of physiological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3R). Current in vitro models lack cell-matrix interactions and their spatiotemporal complexity. To facilitate these analyses, a bone-mimetic template is developed in this study, inspired by bone's extracellular matrix composition and organization. Silk fibroin (SF) is used as an organic matrix, poly-aspartic acid (pAsp) is used to mimic the functionality of noncollagenous proteins, and 10× simulated body fluid serves as mineralization solution. By using pAsp in the mineralization solution, minerals are guided toward the SF material resulting in mineralization inside and as a coating on top of the SF. After cytocompatibility testing, remodeling experiments are performed in which mineralized scaffold remodeling by osteoclasts and osteoblasts is tracked with nondestructive microcomputed tomography and medium analyses over a period of 42 d. The mineralized scaffolds support osteoclastic resorption and osteoblastic mineralization, in the physiological bone remodeling specific sequence. This model could therefore facilitate the investigation of cell-matrix interactions and may thus reduce animal experiments and advance in vitro drug testing for bone remodeling pathologies like osteoporosis, where cell-matrix interactions need to be targeted.

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Measuring mineralised tissue formation and resorption in a human 3D osteoblast-osteoclast co-culture model

Cited by 15 publications

References 38 publications

Osteoblast-osteoclast co-cultures: A systematic review and map of available literature

Osteoblast-osteoclast co-cultures: A systematic review and map of available literature

Osteoblast-osteoclast co-cultures: a systematic review and map of available literature

Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models

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