Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. HIF1 is known to be a positive regulator of bone formation. Conversely, the role of HIF2 in the control osteoblast biology is still poorly understood. In this study, we used mouse genetics to demonstrate that HIF2 is an inhibitor of osteoblastogenesis and bone mass accrual. Moreover, we provided evidence that HIF2 impairs osteoblast differentiation at least in part, by upregulating the transcription factor Sox9. Our findings constitute a paradigm shift, as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone formation through HIF1. Inhibiting HIF2 could thus represent a therapeutic approach for the treatment of the low bone mass observed in chronic diseases, osteoporosis, or aging.

No abstract

Oxygen (O 2 ) is both an indispensable metabolic substrate and a regulatory signal that controls the activity of Hypoxia-Inducible Factor 1a (Hif1a), a mediator of the cellular adaptation to low O 2 tension (hypoxia). Hypoxic cells require Hif1a to survive. Additionally, Hif1a is an inhibitor of mitochondrial respiration. Hence, we hypothesized that enhancing mitochondrial respiration is detrimental to the survival of hypoxic cells in vivo. We tested this hypothesis in the fetal growth plate, which is hypoxic. Our findings show that mitochondrial respiration is dispensable for survival of growth plate chondrocytes. Furthermore, its impairment prevents the extreme hypoxia and the massive chondrocyte death observed in growth plates lacking Hif1a. Consequently, augmenting mitochondrial respiration affects the survival of hypoxic chondrocytes by, at least in part, increasing intracellular hypoxia. We thus propose that partial suppression of mitochondrial respiration is crucial during development to protect the tissues that are physiologically hypoxic from lethal intracellular anoxia.

An innovative farmers’ market incentive program designed specifically for children was implemented to address persistent challenges with accessing fresh, nutrient-rich foods in a food desert community. The current study sought to qualitatively examine caregiver perceptions of the incentive program. Following distribution of farmers’ market incentives to all children (ages 0 to 15 years) at 43 Flint-area early childcare facilities and elementary schools, researchers conducted semistructured interviews with 37 caregivers (mean age = 39.59 ± 11.73 years). The majority were female (87%) and African American (53%). Through these interviews, researchers explored family experiences with the farmers’ market incentive program, as well as changes in environmental factors that may have resulted from program participation. Interviews were audio recorded and transcribed verbatim for textual analysis. Thematic analysis was used to identify patterns across transcripts and formulate emerging themes. Four recurrent themes emerged during interviews: (1) fruit and vegetable access, (2) child influence, (3) autonomous grocery shopping, and (4) program expansion. Interview participants indicated that the farmers’ market incentive program was an effective tool to both encourage families to visit the farmers’ market and purchase fresh foods there. Program design, particularly distribution to children, was credited with introducing families to the local farmers’ market. The current study suggests that a farmers’ market incentive program targeting children who reside in a food desert community may have meaningful impacts on access to fresh, nutrient-rich foods.