Erythropoietin is essential for bone marrow erythropoiesis and erythropoietin receptor on non-erythroid cells including bone marrow stromal cells suggests systemic effects of erythropoietin. Tg6 mice with chronic erythropoietin overexpression have a high hematocrit, reduced trabecular and cortical bone and bone marrow adipocytes, and decreased bone morphogenic protein 2 driven ectopic bone and adipocyte formation. Erythropoietin treatment (1 200 IU·kg^–1) for 10 days similarly exhibit increased hematocrit, reduced bone and bone marrow adipocytes without increased osteoclasts, and reduced bone morphogenic protein signaling in the bone marrow. Interestingly, endogenous erythropoietin is required for normal differentiation of bone marrow stromal cells to osteoblasts and bone marrow adipocytes. ΔEpoR_E mice with erythroid restricted erythropoietin receptor exhibit reduced trabecular bone, increased bone marrow adipocytes, and decreased bone morphogenic protein 2 ectopic bone formation. Erythropoietin treated ΔEpoR_E mice achieved hematocrit similar to wild-type mice without reduced bone, suggesting that bone reduction with erythropoietin treatment is associated with non-erythropoietic erythropoietin response. Bone marrow stromal cells from wild-type, Tg6, and ΔEpoR_E-mice were transplanted into immunodeficient mice to assess development into a bone/marrow organ. Like endogenous bone formation, Tg6 bone marrow cells exhibited reduced differentiation to bone and adipocytes indicating that high erythropoietin inhibits osteogenesis and adipogenesis, while ΔEpoR_E bone marrow cells formed ectopic bones with reduced trabecular regions and increased adipocytes, indicating that loss of erythropoietin signaling favors adipogenesis at the expense of osteogenesis. In summary, endogenous erythropoietin signaling regulates bone marrow stromal cell fate and aberrant erythropoietin levels result in their impaired differentiation.

促红细胞生成素对于骨髓促红细胞生成是必不可少的，并且促红细胞生成素在包括骨髓基质细胞在内的非促红细胞上的受体表明促红细胞生成素的全身作用。慢性促红细胞生成素过表达的Tg6小鼠具有较高的血细胞比容，小梁和皮质骨以及骨髓脂肪细胞减少，并且由骨形态发生蛋白2驱动的异位骨和脂肪细胞形成减少。促红细胞生成素治疗（1200 IU·kg ^–1）持续10天同样表现出血细胞比容增加，骨骼和骨髓脂肪细胞减少而破骨细胞没有增加，以及骨髓中骨形态发生蛋白信号的减少。有趣的是，内源性促红细胞生成素是骨髓基质细胞向成骨细胞和骨髓脂肪细胞正常分化所必需的。ΔEpoR _è红细胞限制型促红细胞生成素受体的小鼠表现出骨小梁减少，骨髓脂肪细胞增加以及骨形态发生蛋白2异位骨形成减少。促红细胞生成素治疗的ΔEpoR _Ë小鼠血细胞比容达到类似于野生型小鼠没有减少骨，提示骨还原促红细胞生成素治疗与非红细胞生成的红细胞生成素的响应相关联。从野生型，TG6，和ΔEpoR骨髓基质细胞_ë -mice移植到免疫缺陷小鼠，以评估发展成骨/骨髓的器官。像内源性骨形成，TG6骨髓细胞减少表现出分化成骨细胞和脂肪细胞，表明高抑制促红细胞生成素和骨生成脂肪生成，而ΔEpoR _È骨髓细胞形成异位骨，其骨小梁区域减少，脂肪细胞增加，这表明促红细胞生成素信号的丧失有利于脂肪形成，但会损害成骨作用。总之，内源性促红细胞生成素信号传导调节骨髓基质细胞的命运，异常的促红细胞生成素水平导致其分化受损。