Bone Marrow, Cytokines, and Bone Remodeling — Emerging Insights into the Pathophysiology of Osteoporosis

Abstract

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.

Effects of vitamin E on bone turnover markers among US postmenopausal women

“…(69) Furthermore, gamma tocopherol and its metabolites may inhibit proinflammatory cytokines that induce osteoclast differentiation. (70) Therefore, it is possible that gamma-tocopherol may stimulate bone formation without increasing bone resorption. Few animal studies have examined the effects of alphatocopherol supplementation on bone health but their results are conflicting.…”

dlk1/FA1 Regulates the Function of Human Bone Marrow Mesenchymal Stem Cells by Modulating Gene Expression of Pro-inflammatory Cytokines and Immune Response-related Factors

“…IL-1␣, IL-1␤, and IL-6, have been shown by others to inhibit osteoblast cell differentiation and to potentiate bone resorption (64) and are associated with osteoporotic bone loss in a variety of diseases, e.g. rheumatoid arthritis (65,66). The possible role of dlk1 in these diseases remains to be determined.…”

Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathway

“…The inability of RANK to bind RANKL leads to the inhibition of osteoclast differentiation and maturation, thereby causing a deficiency of mature osteoclasts at the bone surface [19] . In addition, other cytokines that mediate bone remodeling, such as monocyte-macrophage colony stimulating factor (M-CSF), are also known to promote osteoclastogenesis [20] .…”