Lipid availability determines fate of skeletal progenitor cells via SOX9

Gastel, Nick van; Stegen, Steve; Eelen, Guy; Schoors, Sandra; Carlier, Aurélie; Daniëls, Veerle W.; Baryawno, Ninib; Przybylski, Dariusz; Depypere, Maarten; Stiers, Pieter-Jan; Lambrechts, Dennis; Looveren, Riet Van; Torrekens, Sophie; Sharda, Azeem; Agostinis, Patrizia; Lambrechts, Diether; Maes, Frederik; Swinnen, Johan; Geris, Liesbet; Oosterwyck, Hans Van; Thienpont, Bernard; Carmeliet, Peter; Scadden, David T.; Carmeliet, Geert

doi:10.1038/s41586-020-2050-1

Cited by 171 publications

(155 citation statements)

References 57 publications

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“…(107,108) Interestingly, the obstruction of vascular invasion during bone healing favors chondrogenic over osteogenic differentiation of skeletal progenitor cells, which is driven by SOX9 acting as a regulator of cellular metabolism by suppressing oxidation of fatty acids. (109) During bone repair, several pro-angiogenic and angiocrine factors participate in inducing vascularisation and new bone growth. For instance, VEGFA is an essential proangiogenic factor that promotes bone repair.…”

Section: Role Of Bone Vasculature In Bone Repair and Regenerationmentioning

confidence: 99%

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Chen

Hendriks

Chatzis

et al. 2020

Journal of Bone and Mineral Research

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Bone vasculature and bone marrow vascular niches supply oxygen, nutrients, and secrete angiocrine factors required for the survival, maintenance, and self-renewal of stem and progenitor cells. In the skeletal system, vasculature creates nurturing niches for bone and blood-forming stem cells. Blood vessels regulate hematopoiesis and drive bone formation during development, repair, and regeneration. Dysfunctional vascular niches induce skeletal aging, bone diseases, and hematological disorders. Recent cellular and molecular characterization of the bone marrow microenvironment has provided unprecedented insights into the complexity, heterogeneity, and functions of the bone vasculature and vascular niches. The bone vasculature is composed of distinct vessel subtypes that differentially regulate osteogenesis, hematopoiesis, and disease conditions in bones. Further, bone marrow vascular niches supporting stem cells are often complex microenvironments involving multiple different cell populations and vessel subtypes. This review provides an overview of the emerging vascular cell heterogeneity in bone and the new roles of the bone vasculature and associated vascular niches in health and disease.

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Section: Role Of Bone Vasculature In Bone Repair and Regenerationmentioning

confidence: 99%

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Chen

Hendriks

Chatzis

et al. 2020

Journal of Bone and Mineral Research

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show abstract

“…al. (40) identified a role for fatty acid utilization during fracture healing and the specification of skeletal cell fate. During the bone healing process, endochondral ossification is initiated by periosteal progenitor cells that differentiate to chondrocytes and form an avascular, cartilaginous callus.…”

Section: Requirement For Fatty Acid Oxidation In Osteoblastsmentioning

confidence: 99%

“…al. (40) reported that chondrocytes express low levels of CPT1a and high Glut1 levels as well as elevated lactate production, which suggests that glycolysis meets the chondrocyte's energy needs. On the other hand, osteoblasts expressed high levels of Glut1 and CPT1a, exhibited higher levels of oxygen consumption, and an increased ability to metabolize palmitate, indicating a reliance on fatty acid oxdiation.…”

Section: Requirement For Fatty Acid Oxidation In Osteoblastsmentioning

confidence: 99%

“…This figure was created using Servier Medical Art image templates under a Creative Commons Attribution 3.0 Unported License. the importance of fatty acid catabolism for normal bone formation (39,40), but detrimental effects of lipids on osteoblast performance are also well-known (41,42). In this review, we discuss the dual effects of lipids on osteoblast function and the maintenance of bone mass and strength.…”

Section: Introductionmentioning

confidence: 99%

“…While lipid metabolism yields significantly more ATP than glucose or glutamine catabolism, its role in osteoblast function remains more controversial. Recent studies have highlighted the importance of fatty acid catabolism for normal bone formation ( 39 , 40 ), but detrimental effects of lipids on osteoblast performance are also well-known ( 41 , 42 ). In this review, we discuss the dual effects of lipids on osteoblast function and the maintenance of bone mass and strength.…”

Section: Introductionmentioning

confidence: 99%

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Dual Effects of Lipid Metabolism on Osteoblast Function

2020

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The skeleton is a dynamic and metabolically active organ with the capacity to influence whole body metabolism. This newly recognized function has propagated interest in the connection between bone health and metabolic dysfunction. Osteoblasts, the specialized mesenchymal cells responsible for the production of bone matrix and mineralization, rely on multiple fuel sources. The utilization of glucose by osteoblasts has long been a focus of research, however, lipids and their derivatives, are increasingly recognized as a vital energy source. Osteoblasts possess the necessary receptors and catabolic enzymes for internalization and utilization of circulating lipids. Disruption of these processes can impair osteoblast function, resulting in skeletal deficits while simultaneously altering whole body lipid homeostasis. This article provides an overview of the metabolism of postprandial and stored lipids and the osteoblast's ability to acquire and utilize these molecules. We focus on the requirement for fatty acid oxidation and the pathways regulating this function as well as the negative impact of dyslipidemia on the osteoblast and skeletal health. These findings provide key insights into the nuances of lipid metabolism in influencing skeletal homeostasis which are critical to appreciate the extent of the osteoblast's role in metabolic homeostasis.

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3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host‐To‐Implant Perfusion

et al. 2021

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Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel‐like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel‐like scaffolds and endothelial cells seeded in their lumen form native‐like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native‐like millimetric vessels. This work presents a novel strategy aiming to create fully‐engineered patient‐specific thick tissue flaps.

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Lipid availability determines fate of skeletal progenitor cells via SOX9

Cited by 171 publications

References 57 publications

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease

Dual Effects of Lipid Metabolism on Osteoblast Function

3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host‐To‐Implant Perfusion

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