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Biology Articles » Anatomy & Physiology » Nothing but skin and bone » The hematopoietic stem cell niche

The hematopoietic stem cell niche
- Nothing but skin and bone

In the Review by Tong Yin and Linheng Li (46), the authors summarizeanother new and exciting arena in bone biology, the HSC niche.The model, proposed simultaneously by Li and coworkers and Calviet al. (47, 48) suggests that mesenchymal cells, in the formof bone-lining osteoblasts, are central to the maintenance ofHSCs and their proliferation and/or differentiation. The systemis complex since (a) many ligands and receptors that modulateinteraction between myeloid and mesenchymal cells and henceexpression of paracrine factors are present on both cell typesand (b) many of the ligands and/or receptors are themselvesregulated by cytokines. The authors also summarize data suggestingthat bone marrow endothelium acts as a niche for a functionallydistinct cell population. In related findings, the work of Brandiand Collin-Osdoby indicates that vascular endothelial cellsrespond to inflammatory cytokines by secreting receptor activatorof NF-κB ligand (RANKL) and chemokines that are chemoattractivefor osteoclast precursors and augment the osteoclastogenic capacityof RANKL (49).

Bone marrow is also the environment in which specific metastasesmanifest their osteolytic and/or osteogenic phenotypes. Cancercells facilitate their infiltration into the marrow cavity bystimulating osteoclast formation and function. An initial stimulusis PTHrP generation by lung and breast cancer cells (50-52),thus enhancing mesenchymal production of RANKL and M-CSF whiledecreasing that of OPG (see Osteoclast biology). The resultingincrease in matrix dissolution releases bone-residing cytokinesand growth factors that, by feedback mechanisms, increase growthand/or survival of cancer cells. This loop has been termed "thevicious cycle" (Figure 2) (51). Multiple myeloma uses a differentbut related strategy, namely secretion of macrophage inhibitoryprotein 1α (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1),both of which are chemotactic and proliferative for osteoclastprecursors (53, 54). Metastasis of prostate cancer to bone hasboth lytic and blastic components, with the net result beingdeposition of excess woven bone (55). A recent study suggeststhat BMP-6, produced by cancer cells, stimulates their invasiveand proliferative capacity (56). Similarly, inhibition of VEGFalso blunts prostate metastasis (57), suggesting that multiplecytokines play a role in proliferation and invasion of thiscancer. Future studies will undoubtedly reveal additional moleculesmediating bone loss in metastatic disease.


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