Naoki Kubota | PubMed Health

PubMed2006

Increased mobilization of c-kit+ Sca-1+ Lin- (KSL) cells and colony-forming units in spleen (CFU-S) following de novo formation of a stem cell niche depends on dynamic, but not stable, membranous ossification.

Stem cells are thought to inhabit in a unique microenvironment, known as "niche," in which they undergo asymmetric cell divisions that results in reproducing both stem cells and progenies to maintain various tissues throughout life. The cells of osteoblastic lineage have been identified as a key participant in regulating the number of hematopoietic stem cells (HSCs). HSCs receive their regulatory messages from the microenvironment in the bone marrow. This would account for a reason why the localization of hematopoiesis is usually restricted in the bone marrow. To clarify the above possibility we employed a cell implantation-based strategy with a unique osteoblast cell line (KUSA-A1) derived from a C3H/He mouse. The implantation of KUSA-A 1 cells resulted in the generation of ectopic bones in the subcutaneous tissues of the athymic BALB/c nu/nu mice. Subsequently the mice obtained a greater amount of the bone marrow than normal mice, and they showed an increased number of HSCs. These results indicate that the newly generated osteoblasts-derived ectopic bones are responsible for the increase in the number of the HSC population. Furthermore, the increased number of HSCs directly correlates with both the magnitude of dynamic osteogenic process and the size of the newly generated bone or "niche."

Animals↗

PubMed2005

[Vitamin D and bone quality].

Active vitamin D analogs such as alfacalcidol have been shown to reduce fracture risk in clinical trials in spite of its moderate effects on bone mass. It has been reported that active vitamin D analogs may improve bone quality, by amelioration of bone microarchitecture, by specific effect on cortical bones, by acceleration of calcification, and by effect on nature of bone matrix proteins. The bone quality assessments that clarify the effect on bone mechanical properties will become important for the positioning of osteoporosis drugs.

Animals↗

PubMedDate not supplied

Receptor microscopic autoradiography for the study of percutaneous absorption, in vivo skin penetration, and cellular-intercellular deposition.

INTRODUCTION: Microscopic autoradiography with cellular resolution and preservation of in vivo conditions is potentially the method of choice to gain detailed information about sites of deposition and retention in the epidermis and of penetration to the dermis after topical application of drugs. We tested this using (3)H-Maxacalcitol. METHODS: Dorsal skin of adult rats was treated in vivo with ointment containing 1 or 40 microg/kg body weight of the vitamin D analogue (3)H-Maxacalcitol for periods of 0.5, 2, 8, 24, 48, or 168 h. Samples of skin exposed to the ointment and control samples remote from the treatment site were excised and freeze-mounted, and 4-microm frozen sections were exposed to nuclear emulsion. RESULTS: Two penetration routes to the dermis could be distinguished: one via epidermal cell layers and the other via hair follicles. Highest uptake and retention of radiolabeled steroid was observed in stratum corneum and in intercellular spaces of stratum granulosum. By contrast, cell boundaries and intercellular spaces in the stratum spinosum and basale contained low levels of radioactivity. Keratinocytes in these layers showed high concentration in the cytoplasm at early time intervals, when surrounding radioactivity levels were high, but high nuclear and low or no cytoplasmic concentration at late time intervals, when surrounding radioactivity levels were low. DISCUSSION: The autoradiographic method provides detailed information on time- and dose-related distribution of radiolabeled compound at the cellular level that is not obtainable with common radioassays and biochemical procedures. A sustained concentration and retention of radiolabeled steroid in the stratum corneum and intercellular space of the stratum granulosum indicate a selective deposition in components of secreted-membrane-coating granules and suggest a temporary barrier and depot for slow release. The differential cytoplasmic-nuclear distribution in the stratum Malpighi suggests functional correlation to a toxic-hormetic reversal of action on cell proliferation, from high-dose inhibitory effects associated with high extranuclear concentration as utilized in the treatment of psoriasis, to low-dose stimulatory effects associated with high nuclear and low cytoplasmic concentration as applicable in wound healing.

Administration, Topical↗