総説・解説等

Osteocytes and their dendrites form a large network called the lacuno-canalicular system in mammalian bone. Osteocytes are believed to directly contribute to regulation of mineralization and demineralization in bone matrix, in addition to their indirect regulation of these processes through osteoblasts and osteoclasts. Not only can the location and shape of osteocyte lacunae and canaliculi be spatially visualized in isolated bone samples using synchrotron radiation technology, but differences in the degree of mineralization throughout the lacuno-canalicular system can be detected and quantified. Currently, comparable observation of the time course of these activities in vivo is technically challenging. This review provides an overview of non-dynamic quantitative analysis in the lacuno-canalicular system. Such analysis has the potential to become a methodological basis for investigating osteocyte-dependent direct regulation of mineralization in bone diseases.

In bones, aging manifests itself as a shift towards production of myeloid cells in bone marrow, a condition associated with increased chronic inflammation by macrophages and decreased bone mass due to excess bone resorption by osteoclasts. An increase in the ratio of RANKL, a cytokine promoting osteoclast differentiation, to osteoprotegerin (OPG) , which acts as a decoy RANKL receptor, cannot explain the observed increase in osteoclast production, as serum OPG levels increase with age in humans, apparently to levels insufficient to counteract bone loss and prevent fracture. Age-related increases in osteoclastogenesis, decreases in lymphopoiesis, and inflammation including arthritis are likely best explained by a vicious cycle of myeloid skewing and inflammation occurring in bone marrow. These activities are due to aging of both hematopoietic stem cells themselves and the bone marrow microenvironment (niche cells) , which supports hematopoiesis. Impaired osteoblastogenesis and niche cell function are most likely pathologies emerging from increased oxidative stress, peroxisome proliferator-activated receptorγ (PPARγ) activity, and adipogenesis in the aging bone marrow. Currently, administration of either OPG or an anti-RANKL antibody has proved beneficial to prevent block bone dysfunction and osteoporosis in the elderly. However, anti-aging interventions targeting mesenchymal stem cell differentiation in the bone marrow may also help counteract inflammation and osteoclastic bone loss and enhance osteoblastic bone formation.

Osteocytes are present in osteocytic lacunae in both cortical and trabecular bone, where they are interconnected by numerous dendrites in osteocytic canaliculi. In mammals, osteocytes are the most abundant bone cells, outnumbering osteoclasts and osteoblasts. Osteoclasts are the primary bone-resorbing cells ; however, the concept that osteocytes resorb bone by a process called osteocytic osteolysis has been postulated to explain dynamic calcium release from bone in conditions as diverse as parathyroid hormone (PTH) stimulation, hibernation, glucocorticoid stimulation, and lactation. Osteocytic osteolysis remains a controversial concept, mainly because it is difficult to demonstrate experimentally. Recently, novel functions of osteocytes in mineral metabolism and bone remodeling have been reported, and osteocytic osteolysis is being examined more closely experimentally. This review discusses published literature relevant to osteocytic osteolysis and compares 2D and 3D measurements of the volume of osteocytic lacunae, which serve as anatomical evidence for "periosteocytic osteolysis" .