Manolagas S C, Jilka R L
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
N Engl J Med. 1995 Feb 2;332(5):305-11. doi: 10.1056/NEJM199502023320506.
Both osteoblasts and osteoclasts are derived from progenitors that reside in the bone marrow; osteoblasts belong to the mesenchymal lineage of the marrow stroma, and osteoclasts to the hematopoietic lineage. The development of osteoclasts from their progenitors is dependent on stromal-osteoblastic cells, which are a major source of cytokines that are critical in osteoclastogenesis, such as interleukin-6 and interleukin-11. The production of interleukin-6 by stromal osteoblastic cells, as well as the responsiveness of bone marrow cells to cytokines such as interleukin-6 and interleukin-11, is regulated by sex steroids. When gonadal function is lost, the formation of osteoclasts as well as osteoblasts increases in the marrow, both changes apparently mediated by an increase in the production of interleukin-6 and perhaps by an increase in the responsiveness of bone marrow progenitor cells not only to interleukin-6 but also to other cytokines with osteoclastogenic and osteoblastogenic properties. The cellular activity of the bone marrow is also altered by the process of aging. Specifically, senescence may decrease the ability of the marrow to form osteoblast precursors. The association between the dysregulation of osteoclast or osteoblast development in the marrow and the disruption of the balance between bone resorption and bone formation, resulting in the loss of bone, leads to the following notion. Like homeostasis of other regenerating tissues, homeostasis of bone depends on the orderly replenishment of its cellular constituents. Excessive osteoclastogenesis and inadequate osteoblastogenesis are responsible for the mismatch between the formation and resorption of bone in postmenopausal and age-related osteopenia. The recognition that changes in the numbers of bone cells, rather than changes in the activity of individual cells, form the pathogenetic basis of osteoporosis is a major advance in understanding the mechanism of this disease.
成骨细胞和破骨细胞均起源于存在于骨髓中的祖细胞；成骨细胞属于骨髓基质的间充质谱系，而破骨细胞属于造血谱系。破骨细胞从其祖细胞发育而来依赖于基质成骨细胞，基质成骨细胞是细胞因子的主要来源，这些细胞因子在破骨细胞生成中至关重要，如白细胞介素 - 6和白细胞介素 - 11。基质成骨细胞产生白细胞介素 - 6，以及骨髓细胞对白细胞介素 - 6和白细胞介素 - 11等细胞因子的反应性，均受性类固醇调节。当性腺功能丧失时，骨髓中破骨细胞以及成骨细胞的形成均增加，这两种变化显然是由白细胞介素 - 6产生的增加介导的，也许还由骨髓祖细胞不仅对白细胞介素 - 6而且对其他具有破骨细胞生成和成骨细胞生成特性的细胞因子反应性的增加介导。骨髓的细胞活性也会因衰老过程而改变。具体而言，衰老可能会降低骨髓形成成骨细胞前体的能力。骨髓中破骨细胞或成骨细胞发育失调与骨吸收和骨形成之间平衡的破坏（导致骨质流失）之间的关联，引出了以下观点。与其他再生组织的稳态一样，骨的稳态取决于其细胞成分的有序补充。绝经后和与年龄相关的骨质减少中，破骨细胞生成过多和成骨细胞生成不足是骨形成与吸收不匹配的原因。认识到骨细胞数量的变化而非单个细胞活性的变化构成骨质疏松症的发病基础，是理解该疾病机制的一项重大进展。
