RESUMO
Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors1-6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7-12, although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin13,14, distinguishes peri-arteriolar LEPR+ cells poised to undergo osteogenesis from peri-sinusoidal LEPR+ cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR+osteolectin+ cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin+ cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin+ cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin+ cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin+ cells depleted osteolectin+ cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing.
Assuntos
Arteríolas , Linfopoese , Osteogênese , Nicho de Células-Tronco , Tecido Adiposo/citologia , Envelhecimento , Animais , Células da Medula Óssea/citologia , Osso e Ossos/citologia , Feminino , Fatores de Crescimento de Células Hematopoéticas/metabolismo , Lectinas Tipo C/metabolismo , Linfócitos/citologia , Masculino , Camundongos , Receptores para Leptina/metabolismo , Fator de Células-Tronco , Células Estromais/citologiaRESUMO
The behaviour of M. leprae in fat tissue was studied. Preadipocyte cells were infected with M. leprae and injected intradermally (I.D.) into nude mice. Adipose nodules obtained by in vivo differentiation of infected cells were maintained in vivo for 3 months and subsequently incubated in vitro for 3 months. Counts of bacilli showed no increase over this 6 months period. It is concluded that undifferentiated preadipocyte and mature fat cells are not permissive for M. leprae. The morphological changes observed following passage of M. leprae into adipose nodules might be related to the process of adipose cell differentiation.