The burden of hip fracture is illustrated by the high incidence of postfracture disability and the high mortality rate in both men and women. Nevertheless, few men receive antiresorptive treatment.
The factors contributing to heterotopic ossification, the formation of bone in abnormal soft-tissue locations, are beginning to emerge, but little is known about microenvironmental conditions promoting this often devastating disease. Using a murine model in which endochondral bone formation is triggered in muscle by bone morphogenetic protein 2 (BMP2), we studied changes near the site of injection of BMP2-expressing cells. As early as 24 hours later, brown adipocytes began accumulating in the lesional area. These cells stained positively for pimonidazole and therefore generated hypoxic stress within the target tissue, a prerequisite for the differentiation of stem cells to chondrocytes and subsequent heterotopic bone formation. We propose that aberrant expression of BMPs in soft tissue stimulates production of brown adipocytes, which drive the early steps of heterotopic endochondral ossification by lowering oxygen tension in adjacent tissue, creating the correct environment for chondrogenesis. Results in misty gray lean mutant mice not producing brown fat suggest that white adipocytes convert into fat-oxidizing cells when brown adipocytes are unavailable, providing a compensatory mechanism for generation of a hypoxic microenvironment. Manipulation of the transcriptional control of adipocyte fate in local softtissue environments may offer a means to prevent or treat development of bone in extraskeletal sites. (Am
By indirect immunofluorescence techniques, microtubules and mitochondria were localized in normal rat kidney cells, human WI38 fibroblasts, mouse peritoneal macrophages, and a putative smooth muscle rat cell line, in monolayer culture. The mitochondria were found to be arranged along the cytoplasmic microtubules in each cell type. Disruption of the microtubules with colcemid caused a redistribution of the mitochondria in these cells. There was no correlation between the location of the mitochondria and actin-containing filaments. This evidence suggests that mitochondria are directly or indirectly associated with microtubules in these cells.The control mechanisms that determine the location and movement of intracellular organelles are not well understood. Microtubules have often been implicated in such phenomena, particularly in connection with membrane-bound intracellular organelles. By now, the literature on this subject is too voluminous to cite adequately; as examples, see refs. 1-6. In the present paper, we confine our attention to possible interactions between microtubules and mitochondria. The most impressive previous evidence for the existence of such interactions has come from electron microscopic studies of neuronal axons (7,8). In these elongated cell processes viewed in cross sections, the proximity of mitochondria to microtubules has been shown statistically to be much greater than expected from a random distribution; furthermore, by heavy positive staining, what appear to be cross bridges between microtubules and proximal mitochondria have been demonstrated. These studies, however, leave open the question whether these microtubular-mitochondrial interactions are general to all cells or only to highly specialized axonal processes, as well as many other questions relating to the detailed mechanisms and possible functions of such interactions. Furthermore, the thin-section electron microscopic method for detecting such interactions is feasible only with oriented cell processes such as axons, and, at least intially, other methods are required for the more general case.During studies from this laboratory on the fluorescence staining of specific intracellular components, we have obtained clear evidence at the light microscopic level of resolution for an association between microtubules and mitochondria in several unrelated types of cultured cells. This evidence is presented in this paper. MATERIALS AND METHODSAntitubulin Antibodies. Tubulin was prepared from 12-day-old chick embryo brain by the disaggregation-reaggregation method of Shelanski et al. (9). The preparations that were used for immunization had a relatively small amount of microtubule-associated protein in addition to microtubule protein. The animals were immunized by a modification of the procedure described by Van Vunakis et al. (10). The protein (1.0 mg) was mixed with an equal weight of methylated bovine serum albumin and Freund's complete adjuvant and injected in the toe pads and foot pads of New Zealand white rabbits. After 3 we...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.