BackgroundThe fully developed adult skeleton adapts to mechanical forces by generating more bone, usually at the periosteal surface. Progenitor cells in the periosteum are believed to differentiate into bone-forming osteoblasts that contribute to load-induced adult bone formation, but in vivo evidence does not yet exist. Furthermore, the mechanism by which periosteal progenitors might sense physical loading and trigger differentiation is unknown. We propose that periosteal osteochondroprogenitors (OCPs) directly sense mechanical load and differentiate into bone-forming osteoblasts via their primary cilia, mechanosensory organelles known to be involved in osteogenic differentiation.MethodsWe generated a diphtheria toxin ablation mouse model and performed ulnar loading and dynamic histomorphometry to quantify the contribution of periosteal OCPs in adult bone formation in vivo. We also generated a primary cilium knockout model and isolated periosteal cells to study the role of the cilium in periosteal OCP mechanosensing in vitro. Experimental groups were compared using one-way analysis of variance or student’s t test, and sample size was determined to achieve a minimum power of 80%.ResultsMice without periosteal OCPs had severely attenuated mechanically induced bone formation and lacked the mineralization necessary for daily skeletal maintenance. Our in vitro results demonstrate that OCPs in the periosteum uniquely sense fluid shear and exhibit changes in osteogenic markers consistent with osteoblast differentiation; however, this response is essentially lost when the primary cilium is absent.ConclusionsCombined, our data show that periosteal progenitors are a mechanosensitive cell source that significantly contribute to adult skeletal maintenance. More importantly, an OCP population persists in the adult skeleton and these cells, as well as their cilia, are promising targets for bone regeneration strategies.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0930-1) contains supplementary material, which is available to authorized users.

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13K + and NO 3 are the major forms of potassium and nitrogen that are absorbed by the roots 14 of most terrestrial plants. In this study, we observed that the close relationship between 15 NO 3 and K + homeostasis was mediated by nitrate transporter1 (NRT1.1) in Arabidopsis. 16 The nrt1.1 mutants lacking NRT1.1 function showed disturbed K + uptake and root-to-17 shoot allocation, especially under K + -limited conditions, and had a yellow-shoot sensitive 18 phenotype on K + -limited medium. The K + uptake and root-to-shoot allocation of these 19 mutants were partially rescued by expressing NRT1.1 in the root epidermis-cortex and 20 central vasculature by using Sultr1;2 and PHO1 promoters, respectively. Furthermore, 21 two-way analysis of variance based on the K + content in nrt1.1-1/akt1, nrt1.1-1/hak5-3, 22 nrt1.1-1/kup7, and nrt1.1-1/skor-2 double mutants and their corresponding single mutants 23 and wild-type plants revealed physiological interactions between NRT1.1 and K + 24 channels located in the root epidermis-cortex and central vasculature. Taken together, 25 these data suggest that the expression of NRT1.1 in the root epidermis-cortex coordinates 26 with K + uptake channels to improve K + uptake, whereas its expression in the root central 27 vasculature coordinates with the channels loading K + into the xylem to facilitate K + 28 allocation from the roots to the shoot.29 30

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