Project description:This a model from the article: A mathematical model of bone remodeling dynamics for normal bone cell populations and myeloma bone disease Bruce P Ayati, Claire M Edwards, Glenn F Webb and John P Wikswo. Biology Direct2010 Apr 20;5(28). 20406449, Abstract: BACKGROUND: Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease. RESULTS: Mathematical models are developed for normal bone remodeling and for the dysregulated bone remodeling that occurs in myeloma bone disease. The models examine the critical signaling between osteoclasts (bone resorption) and osteoblasts (bone formation). The interactions of osteoclasts and osteoblasts are modeled as a system of differential equations for these cell populations, which exhibit stable oscillations in the normal case and unstable oscillations in the myeloma case. In the case of untreated myeloma, osteoclasts increase and osteoblasts decrease, with net bone loss as the tumor grows. The therapeutic effects of targeting both myeloma cells and cells of the bone marrow microenvironment on these dynamics are examined. CONCLUSIONS: The current model accurately reflects myeloma bone disease and illustrates how treatment approaches may be investigated using such computational approaches. Note: The paper describes three models 1) Zero-dimensional Bone Model without Tumour, 2) Zero-dimensional Bone Model with Tumour and 3) Zero-dimensional Bone Model with Tumour and Drug Treatment. This model corresponds to the Zero-dimensional Bone Model without Tumour. Typos in the publication: Equation (4): The first term should be (β1/α1)^(g12/Γ) and not (β2/α2)^(g12/Γ) Equation (14): The first term should be (β1/α1)^(((g12/(1+r12))/Γ) and not (β2/α2)^(((g12/(1+r12))/Γ) Equation (13): The first term should be (β1/α1)^((1-g22+r22)/Γ) and not (β1/α1)^((1-g22-r22)/Γ) All these corrections has been implemented in the model, with the authors agreement. Beyond these, there are several mismatches between the equation numbers that are mentioned in for each equation and the reference that has been made to these equations in the figure legend.

Project description:This a model from the article: A mathematical model of bone remodeling dynamics for normal bone cell populations and myeloma bone disease Bruce P Ayati, Claire M Edwards, Glenn F Webb and John P Wikswo. Biology Direct2010 Apr 20;5(28). 20406449, Abstract: BACKGROUND: Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease. RESULTS: Mathematical models are developed for normal bone remodeling and for the dysregulated bone remodeling that occurs in myeloma bone disease. The models examine the critical signaling between osteoclasts (bone resorption) and osteoblasts (bone formation). The interactions of osteoclasts and osteoblasts are modeled as a system of differential equations for these cell populations, which exhibit stable oscillations in the normal case and unstable oscillations in the myeloma case. In the case of untreated myeloma, osteoclasts increase and osteoblasts decrease, with net bone loss as the tumor grows. The therapeutic effects of targeting both myeloma cells and cells of the bone marrow microenvironment on these dynamics are examined. CONCLUSIONS: The current model accurately reflects myeloma bone disease and illustrates how treatment approaches may be investigated using such computational approaches. Note: The paper describes three models 1) Zero-dimensional Bone Model without Tumour, 2) Zero-dimensional Bone Model with Tumour and 3) Zero-dimensional Bone Model with Tumour and Drug Treatment. This model corresponds to the Zero-dimensional Bone Model with Tumour. Typos in the publication: Equation (4): The first term should be (β1/α1)^(g12/Γ) and not (β2/α2)^(g12/Γ) Equation (14): The first term should be (β1/α1)^(((g12/(1+r12))/Γ) and not (β2/α2)^(((g12/(1+r12))/Γ) Equation (13): The first term should be (β1/α1)^((1-g22+r22)/Γ) and not (β1/α1)^((1-g22-r22)/Γ) All these corrections has been implemented in the model, with the authors agreement. Beyond these, there are several mismatches between the equation numbers that are mentioned in for each equation and the reference that has been made to these equations in the figure legend.

Project description:This a model from the article: A mathematical model of bone remodeling dynamics for normal bone cell populations and myeloma bone disease Bruce P Ayati, Claire M Edwards, Glenn F Webb and John P Wikswo. Biology Direct2010 Apr 20;5(28). 20406449, Abstract: BACKGROUND: Multiple myeloma is a hematologic malignancy associated with the development of a destructive osteolytic bone disease. RESULTS: Mathematical models are developed for normal bone remodeling and for the dysregulated bone remodeling that occurs in myeloma bone disease. The models examine the critical signaling between osteoclasts (bone resorption) and osteoblasts (bone formation). The interactions of osteoclasts and osteoblasts are modeled as a system of differential equations for these cell populations, which exhibit stable oscillations in the normal case and unstable oscillations in the myeloma case. In the case of untreated myeloma, osteoclasts increase and osteoblasts decrease, with net bone loss as the tumor grows. The therapeutic effects of targeting both myeloma cells and cells of the bone marrow microenvironment on these dynamics are examined. CONCLUSIONS: The current model accurately reflects myeloma bone disease and illustrates how treatment approaches may be investigated using such computational approaches. Note: The paper describes three models 1) Zero-dimensional Bone Model without Tumou r, 2) Zero-dimensional Bone Model with Tumour and 3) Zero-dimensional Bone Model with Tumour and Drug Treatment. This model corresponds to the Zero-dimensional Bo ne Model with Tumour and Drug Treatment. Typos in the publication: Equation (4): The first term should be (β1/α1)^(g12/Γ) and not (β2/α2)^(g12/Γ) Equation (14): The first term should be (β1/α1)^(((g12/(1+r12))/Γ) and not (β2/α2)^(((g12/(1+r12))/Γ) Equation (13): The first term should be (β1/α1)^((1-g22+r22)/Γ) and not (β1/α1)^((1-g22-r22)/Γ) All these corrections has been implemented in the model, with the authors agreement. Beyond these, there are several mismatches between the equation numbers that are mentioned in for each equation and the reference that has been made to these equations in the figure legend.

Project description:The unique properties of the bone marrow allow for migration and proliferation of multipl myeloma (MM) cells, while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. Bone marrow adipocytes (BMAds), which have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary bone marrow cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and reciprocally, BMAds support MM cells in vitro. Importantly, most data investigating BMAds have been generated using adipocytes derived by differentiating bone marrow-derived mesenchymal stromal cells (MSCs) into adipocytes in vitro using adipogenic media, due to the extreme technical challenges associated with isolating and culturing primary adipocytes. However, if studies could be performed with primary adipocytes, they likely will recapitulate in vivo biology better than MSC-derived adipocyte, as the differentiation process is artificial and differs from in vivo differentiation, and progenitor cell(s) of the primary BMAd may not be the same as the MSCs precursors used for adipogenic differentiation in vitro. Therefore, we developed and refined three methods for culturing primary BMAds (pBMAds): 2D coverslips, 2D transwells, and 3D silk scaffolds, all of which can be cultured alone or with MM cells to investigate bidirectional tumor-host signaling. To develop an in vitro model with a tissue-like structure to mimic the bone marrow microenvironment, we developed the first 3D, tissue engineered model utilizing pBMAds derived from human bone marrow. We found that pBMAds, which are extremely fragile, can be isolated and stably cultured in 2D for 10 days and in 3D for short term (~2 weeks) or long term (1 month) in vitro. To investigate the relationship between pBMAds and myeloma, MM cells can be added to investigate physical relationships through confocal imaging and soluble signaling molecules via mass spectrometry. In sum, we developed three in vitro cell culture systems to study primary bone marrow adipocytes and myeloma cells, which could be adapted to investigate many diseases and biological processes involving the bone marrow, including other bone-homing tumor types.

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