Matrix-Embedded Osteocytes Regulate Mobilization of Hematopoietic Stem/Progenitor Cells

The bone marrow (BM) niche comprises multiple cell types that regulate hematopoietic stem/progenitor cell (HSPC) migration out of the niche and into the circulation. Here, we demonstrate that osteocytes, the major cellular component of mature bone, are regulators of HSPC egress. Granulocyte colony-stimulating factor (G-CSF), used clinically to mobilize HSPCs, induces changes in the morphology and gene expression of the osteocytic network that precedes changes in osteoblasts. This rapid response is likely under control of the sympathetic nervous system, since osteocytes express the β2-adrenergic receptor and surgical sympathectomy prevents it. Mice with targeted ablation of osteocytes or a disrupted osteocyte network have comparable numbers of HSPCs in the BM but fail to mobilize HSPCs in response to G-CSF. Taken together, these results indicate that the BM/bone niche interface is critically controlled from inside of the bone matrix and establish an important physiological role for skeletal tissues in hematopoietic function

A General Framework for the Related-key Linear Attack against Block Ciphers with Linear Key Schedules

We present a general framework for the related-key linear attack that can be applied to iterative block ciphers with linear key schedules. The attack utilizes a newly introduced related-key linear approximation that is obtained directly from a linear trail. The attack makes use of a known related-key data consisting of triplets of a plaintext, a ciphertext, and a key difference such that the ciphertext is the encrypted value of the plaintext under the key that is the xor of the key to be recovered and the specified key difference. If such a block cipher has a linear trail with linear correlation \epsilon, it admits attacks with related-key data of size \epsilon^{-2} just as in the case of classical Matsui\u27s Algorithms. But since the attack makes use of a related-key data, the attacker can use a linear trail with the squared correlation less than 2^{-n}, n being the block size, in case the key size is larger than n. Moreover, the standard key hypotheses seem to be appropriate even when the trail is not dominant as validated by experiments. The attack can be applied in two ways. First, using a linear trail with squared correlation smaller than 2^{-n}, one can get an effective attack covering more rounds than existing attacks against some ciphers, such as Simon48/96, Simon64/128 and Simon128/256. Secondly, using a trail with large squared correlation, one can use related-key data for key recovery even when the data is not suitable for existing linear attacks

Osteocytes Regulate Primary Lymphoid Organs and Fat Metabolism

Osteocytes act as mechanosensors to control local bone volume. However, their roles in the homeostasis of remote organs are largely unknown. We show that ablation of osteocytes in mice (osteocyte-less [OL] mice) leads to severe lymphopenia, due to lack of lymphoid-supporting stroma in both the bone marrow and thymus, and complete loss of white adipose tissues. These effects were reversed when osteocytes were replenished within the bone. In contrast, neither in vivo supply of T cell progenitors and humoral factors via shared circulation with a normal parabiotic partner nor ablation of specific hypothalamic nuclei rescued thymic atrophy and fat loss in OL mice. Furthermore, ablation of the hypothalamus in OL mice led to hepatic steatosis, which was rescued by parabiosis with normal mice. Our results define a role for osteocytes as critical regulators of lymphopoiesis and fat metabolism and suggest that bone acts as a central regulator of multiple organs