Dataset Information

High Mineralization Capacity of IDG-SW3 Cells in 3D Collagen Hydrogel for Bone Healing in Estrogen-Deficient Mice.

ABSTRACT: Tissue engineering with 3D scaffold is a simple and effective method for bone healing after large-scale bone loss. So far, bone marrow-derived mesenchymal stem cells (BMSCs) are mostly used in the treatment of bone healing in animal models due to their self-renewal capability and osteogenic potential. Due to the fact that the main functional cells in promoting osteoid mineralization and bone remodeling were osteocytes, we chose an osteoblast-to-osteocyte transition cell line, IDG-SW3, which are not proliferative under physiological conditions, and compared the healing capability of these cells to that of BMSCs in bone defect. In vitro, IDG-SW3 cells revealed a stronger mineralization capacity when grown in 3D collagen gel, compared to that of BMSCs. Although both BMSC and IDG-SW3 can generate stable calcium-phosphate crystal similar to hydroxyapatite (HA), the content was much more enriched in IDG-SW3-mixed collagen gel. Moreover, the osteoclasts co-cultured with IDG-SW3-mixed collagen gel were easier to be activated, indicating that the IDG-SW3 grafting could promote the bone remodeling more efficiently in vivo. Last, in order to reduce the self-healing capability, we assessed the healing capability between the IDG-SW3 cells and BMSCs in osteoporotic mice. We found that the collagen hydrogel mixed with IDG-SW3 cells has a better healing pattern than what was seen in hydrogel mixed with BMSCs. Therefore, these results demonstrated that by promoting osteoblast-to-osteocyte transition, the therapeutic effect of BMSCs in bone defect repair could be improved.

SUBMITTER: Chen K

PROVIDER: S-EPMC7488085 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

High Mineralization Capacity of IDG-SW3 Cells in 3D Collagen Hydrogel for Bone Healing in Estrogen-Deficient Mice.

Chen Kaizhe K Zhou Qi Q Kang Hui H Yan Yufei Y Qian Niandong N Li Changwei C Wang Fei F Yang Kai K Deng Lianfu L Qi Jin J

Frontiers in bioengineering and biotechnology 20200831

Tissue engineering with 3D scaffold is a simple and effective method for bone healing after large-scale bone loss. So far, bone marrow-derived mesenchymal stem cells (BMSCs) are mostly used in the treatment of bone healing in animal models due to their self-renewal capability and osteogenic potential. Due to the fact that the main functional cells in promoting osteoid mineralization and bone remodeling were osteocytes, we chose an osteoblast-to-osteocyte transition cell line, IDG-SW3, which are ...[more]

PMID: 32984264

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Project description:Excessive FGF23 has been identified as a pivotal phosphaturic factor leading to renal phosphate-wasting and the subsequent development of rickets and osteomalacia. In contrast, loss of FGF23 in mice (Fgf23(-/-) ) leads to high serum phosphate, calcium, and 1,25-vitamin D levels, resulting in early lethality attributable to severe ectopic soft-tissue calcifications and organ failure. Paradoxically, Fgf23(-/-) mice exhibit a severe defect in skeletal mineralization despite high levels of systemic mineral ions and abundant ectopic mineralization, an abnormality that remains largely unexplained. Through use of in situ hybridization, immunohistochemistry, and immunogold labeling coupled with electron microscopy of bone samples, we discovered that expression and accumulation of osteopontin (Opn/OPN) was markedly increased in Fgf23(-/-) mice. These results were confirmed by qPCR analyses of Fgf23(-/-) bones and ELISA measurements of serum OPN. To investigate whether elevated OPN levels were contributing to the bone mineralization defect in Fgf23(-/-) mice, we generated Fgf23(-/-) /Opn(-/-) double-knockout mice (DKO). Biochemical analyses showed that the hypercalcemia and hyperphosphatemia observed in Fgf23(-/-) mice remained unchanged in DKO mice; however, micro-computed tomography (µCT) and histomorphometric analyses showed a significant improvement in total mineralized bone volume. The severe osteoidosis was markedly reduced and a normal mineral apposition rate was present in DKO mice, indicating that increased OPN levels in Fgf23(-/-) mice are at least in part responsible for the osteomalacia. Moreover, the increased OPN levels were significantly decreased upon lowering serum phosphate by feeding a low-phosphate diet or after deletion of NaPi2a, indicating that phosphate levels contribute in part to the high OPN levels in Fgf23(-/-) mice. In summary, our results suggest that increased OPN is an important pathogenic factor mediating the mineralization defect and the alterations in bone metabolism observed in Fgf23(-/-) bones.

Project description:Fibronectin (FN) is an extracellular matrix glycoprotein that is abundantly expressed by fibroblasts in contracting wounds, where it mediates cell adhesion, migration and proliferation. FN also efficiently binds to collagen. Therefore, we and others hypothesized that FN and its cellular receptor integrin α5β1 might be involved in collagen matrix contracture by acting as linkers. However, there are conflicting reports on this issue. Moreover, several publications suggest an important role of collagen-binding integrin receptors α2β1 and α11β1 in collagen matrix contracture. Therefore, the aim of the present study was to determine the contributions of FN-integrin α5β1 interactions relative to those of collagen receptors α2β1 and α11β1 in this process. To assess the role of cellular FN directly, we employed FN-deficient mouse fibroblasts, subjected them to a collagen gel contracture assay in vitro, and compared them to their wildtype counterparts. Exogenous FN was removed from serum-containing medium. For dissecting the role of major collagen receptors, we used two FN-deficient mouse fibroblast lines that both possess integrin α5β1 but differ in their collagen-binding integrins. Embryo-derived FN-null fibroblasts, which express α11- but no α2-integrin, barely spread and tended to cluster on collagen gels. Moreover, FN-null fibroblasts required exogenously added FN to assemble α5β1-integrin in fibrillar adhesion contacts, and to contract collagen matrices. In contrast, postnatal kidney fibroblasts were found to express α2- but barely α11-integrin. When FN expression was suppressed in these cells by shRNA transfection, they were able to spread on and partially contract collagen gels in the absence of exogenous FN. Also in this case, however, collagen contracture was stimulated by adding FN to the medium. Antibody to integrin α5β1 or RGD peptide completely abolished collagen contracture by FN-deficient fibroblasts stimulated by FN addition. We conclude that although collagen-binding integrins (especially α2β1) can mediate contracture of fibrillar collagen gels by murine fibroblasts to some extent, full activity is causally linked to the presence of pericellular FN and its receptor integrin α5β1.

Dataset Information

High Mineralization Capacity of IDG-SW3 Cells in 3D Collagen Hydrogel for Bone Healing in Estrogen-Deficient Mice.

Publications

High Mineralization Capacity of IDG-SW3 Cells in 3D Collagen Hydrogel for Bone Healing in Estrogen-Deficient Mice.

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