Bone might be more solid than other tissues, but it is just as dynamic: maintenance of bone is a constant, balanced process of creation by osteoblast cells and destruction by osteoclast cells. With age, this balance breaks down, however. Osteoblasts accomplish proportionally less work, and osteoclasts accomplish more. As a result, bone becomes weakened, porous, and fragile, leading to the clinical condition of osteoporosis. This is a significant component of frailty and mortality, as fractures and breaks of bone in elderly individuals can happen with little provocation, and when they do, that trauma often marks the beginning of the final spiral downwards.
In seeking to understand osteoporosis, researchers are largely working backwards from the disease state, looking for mechanisms that change the balance of osteoblast and osteoclast cell populations and activity. There are a sizable number of plausible candidates. Chronic inflammation, for example, is thought to be a part of the problem, and it certainly disrupts many other important systems of cellular coordination related to regeneration and tissue maintenance. Senescent cells are a significant source of inflammation in older individuals, and researchers have demonstrated that removing them can partially reverse osteoporosis in mice.
Without a deep examination of the causes, researchers are also mapping changes in the signaling mechanisms by which cells communicate. These communications steer cellular behavior, so in at least some cases it is though that benefits might be obtained by interfering in the signaling responses to the underlying damage of aging, rather than by fixing the damage itself. Much of this signaling is not in the form of molecules secreted unprotected into the intercellular spaces, but rather via vesicles of various types. These are membrane-wrapped packages of molecules, much smaller than cells, and classified by size into classes such as exosomes, microvesicles, and so forth. Research into vesicles is currently blossoming, with scientists hoping to be able to use them to beneficially influence cell behavior in any number of ways. First, however, a certain amount of mapping and experimentation must take place, as is illustrated in this open access paper.
It is worth considering, however, that is probably better to repair the underlying damage that causes signaling changes. That damage causes all sorts of issues, not just the ones that a research team is presently narrowly focused on. It isn't cost-effective, and may not even be possible to intercept and prevent every downstream change without actually repairing the root cause. Here it is hard to even make the argument that all of the important root causes are mysterious and unassailable at this time, given that cellular senescence appears to be significant, and dealing with that via senolytic therapies is almost certainly cheaper right now than working with exosomes.
Normal bone remodeling is activated by osteoclasts that are unique in their function of bone resorption, followed by a constructive process in which new bone is generated by osteoblasts. The coordinated regulation of these important cell types is critical for maintaining physiological bone remodeling, which is tightly controlled by physical cell-cell interactions, secretory signals, and the endocrine system. Osteoclast activation occurs after binding of receptor activator of nuclear factor κB (RANKL) to its receptor RANK, which is expressed in the membrane of osteoclast precursors.
Recent studies have revealed that various key factors involved in bone remodeling are packaged in spherical bilayered membrane vesicles called exosomes. These organelles function as cell-cell communicators by transferring biologically active molecules to adjacent or distant cell. Various cell types secrete exosomes. With an average diameter of 40-150 nm, exosomes are released into the circulation and transfer the biologically active molecules contained within to target cells.
Recent reports indicate the involvement of bone-associated exosomes in regulating bone remodeling, mainly via the transfer of critical molecules required for the regulation of osteoclasts and osteoblasts. However, the comprehensive changes among the proteins in serum-derived exosomes (SDEs) of aged patients with osteoporosis or osteopenia and their functions in bone remodeling remain largely unclear. Here, to determine the biological functions of SDEs in osteoporosis and osteopenia, we compared the proteomic profiles of exosomes purified from the serum of elderly patients with osteoporosis and low bone mass with those of aged and young normal volunteers.
In the present study, we discovered that the SDEs from osteoporosis patients inhibited osteoblastic bone matrix mineralization and promoted osteoclast differentiation. In contrast, SDEs from osteopenia patients enhanced both osteoblast function and osteoclast activation, leading to a compensatory increase in bone remodeling. The SDEs from aged normal volunteers might play a protective role in bone health through facilitating adhesion of bone cells and suppressing aging-associated oxidative stress. The differently expressed proteins identified were involved in different processes and functions intrinsic to bone, including mechanosensation, inflammation, and cell senescence, which are the apparent protagonists in bone remodeling.