ABSTRACT
The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis. MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs' commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.
Subject(s)
Animals , Female , Humans , Adipogenesis/physiology , Bone Marrow Cells/pathology , Mesenchymal Stem Cells/pathology , Osteoporosis/physiopathology , Cells, Cultured , Cell Differentiation/physiology , Osteoblasts/physiology , Osteoclasts/physiologyABSTRACT
Knowledge about the influence of bone on intermediary metabolism corresponds to a developing area that has gained prominence. The old concept of bone and adipose tissues as inert metabolic tissues, with minor contributions to metabolic adaptations has been reconsidered in light of findings that bone is involved in the development of insulin sensitivity. Similarly adipose tissue exerts important influences on bone mass development and maintenance. Moreover, the use of drugs in the treatment of metabolic disorders such as diabetes mellitus can impact bone metabolism. These networks linking osteoporosis to obesity and diabetes mellitus have reinvigorated investigations in the pathophysiology of osteoporosis. The present review examines this aspect and calls attention to health care providers and potential treatments of skeletal disorder.
O estudo sobre a influência do tecido ósseo no metabolismo intermediário corresponde a uma área em desenvolvimento que tem ganho recente destaque. O conceito prévio de que os tecidos ósseo e adiposo seriam metabolicamente inativos foi reconsiderado à luz de estudos que mostram que metabólitos ósseos podem influenciar a sensibilidade à insulina. Da mesma forma, o tecido adiposo exerce influência importante no desenvolvimento e na manutenção da massa óssea. Além disso, o uso de drogas no tratamento de doenças metabólicas como o diabetes melito pode afetar o metabolismo ósseo. A rede de conexões existentes que ligam a osteoporose à obesidade e ao diabetes melito tem revigorado investigações sobre a fisiopatologia da osteoporose. A presente revisão analisa esse aspecto e destaca a necessidade de atenção para esses pontos por parte de serviços de saúde voltados para o atendimento de diabetes melito e da obesidade quanto ao potencial impacto sobre o tecido ósseo.