Mesenchymal Stem Cell Aging as a Contributing Cause of Osteoporosis

Bone tissue is constantly remodeled, broken down by osteoclasts and built up by osteoblasts. With age the balance of activity between these two cell populations shifts to favor osteoclasts. The result is ever weaker and more brittle bones, the condition known as osteoporosis. Numerous mechanisms may contribute to this cellular imbalance, with the signaling of senescent cells clearly implicated on the basis of recent evidence. The open access paper noted here looks another of the possible contributions, the aging of mesenchymal stem cells in the bone marrow.

Aging is a gradual process that results in a loss of tissue homeostasis, driving a progressive deterioration of tissue and organ functions mainly due to cellular damage accumulated throughout life. The human skeleton is especially affected by the passage of time: bone loss begins as early as the third decade of life, immediately after peak bone mass. In humans, bone is a highly active tissue which undergoes continuous self-regeneration throughout adulthood to maintain structural integrity in a process called bone remodeling. It has been estimated that the entire skeleton is remodeled every 10 years.

Throughout young adulthood more bone is formed than is resorbed, resulting in an increase in bone mass. Later on, throughout adulthood when the growth period is finished, the amount of resorbed bone equals that which is subsequently formed (remodeling balance). In the elderly, the amount of bone resorbed is greater than the amount of bone formed; accordingly, a decrease in bone mineral density occurs. As a consequence, bone aging is the main risk factor for primary osteoporosis, characterized by a reduction in bone mineral density, predisposing the elderly population to an increased risk of fractures.

Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells which can be isolated from many tissues and have the capacity of self-renewal and to differentiate into various mesodermal cell types, such as osteoblasts, chondrocytes, and adipocytes. In bone, the process of osteogenesis is driven by a sequential cascade of biological processes initiated by the recruitment of MSCs to bone remodeling sites and subsequent proliferation. During the first steps of differentiation, MSCs proliferate and commit to actively proliferating pre-osteoblasts which do not secrete extracellular matrix (ECM). They further mature into non-proliferating osteoblasts involved in initial matrix secretion, maturation, and mineralization.

In the aging process, bone loss is caused not only by enhanced bone resorption activity but also by functional impairments of MSCs. At the cellular level, the MSC pool in the bone marrow niche shows a biased differentiation into adipogenesis at the cost of osteogenesis. This differentiation shift leads to decreased bone formation, contributing to the etiology of osteoporosis.

Link: https://doi.org/10.1186/s13287-018-0995-x

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