Towards a Better Understanding of Osteoclasts in Osteoporosis

Bone is, despite appearances, a very dynamic tissue. Bone structure is constantly remodeled, and a balance between the activities of osteoblasts that create bone extracellular matrix and osteoclasts that break down that matrix is necessary to maintain healthy, functional bones. With advancing age this balance is disrupted, shifting to favor osteoclast activity over osteoblast activity. Bones become weaker, less dense, and fragile, leading to osteoporosis and serious, life-limiting fracture events.

Given that osteoporosis is an imbalance, there are numerous possible approaches to the development of therapies. Identifying and removing the fundamental causes of reduced osteoblast activity or increased osteoclast activity would be the most likely to succeed. This means reversing or repairing the causative damage and dysfunction of aging. Chronic inflammatory signaling, such as that produced by senescent cells, is likely important, but there are many other contributing causes of aging that likely play a part in the disruption of bone tissue remodeling.

An alternative approach is compensatory: suppress osteoclast activity, or boost osteoblast activity. This is thought to be in principle easier, as any new discovery in the biology of these cells could lead to a therapy, but nonetheless present approaches have yet to produce sizable benefits by using small molecules to manipulate cell behavior. Even given a greater degree of success, compensation will always be less beneficial than addressing the underlying causes of osteoporosis, as those causes lead to many other aspects of aging.

Recent Advances in Osteoclast Biological Behavior

Osteoclasts, as an important component of the bone microenvironment, have always played an irreplaceable role in bone homeostasis. Abnormalities in osteoclast function can lead to abnormal bone resorption. If osteoclasts are hyperfunctional, they can cause degenerative bone diseases such as osteoporosis and osteoarthritis; if they are dysfunctional or declining, they can cause osteosclerosis. Drugs for bone-related diseases affect the process of bone resorption by osteoclasts in three main ways: differentiation, function, and apoptosis. Therefore, we summarize the biological characteristics of osteoclasts in terms of differentiation, apoptosis, behavior changes, and coupling signals with osteoblasts based on previous studies, in this review.

Although we have a more comprehensive understanding of osteoclasts, we still do not know the effects of various modulators on osteoclast behavior in the systemic as well as in the local environment and their mechanisms of action. Additionally, we still have a lot to learn about the processes that control osteoclast sexual dimorphic responses. Research of this phenomena are essential because they can shed light on the pathophysiology of metabolic bone disorders like osteoporosis and how individuals respond to treatment.

The identification of gene targets by understanding these mechanisms may lead to more effective treatments for metabolic diseases of the skeleton. As for coupling signals between osteoclast and osteoblast, rather than simply identifying potential coupling factors, it is time to move on to the next phase. It is imperative that we spend time understanding the kinds of mechanisms that drive the remodeling process, and identify the aspects of those mechanisms that can be used to intervene in human skeletal disorders. Furthermore, we think that interactions existing among macrophages, osteoclasts, and osteoblasts contribute to maintaining bone homeostasis. Therefore, we believe that pathological connections among these cells in disease states and their negative mechanisms will be a new field for further exploration.


"osteoblasts that create bone extracellular matrix and osteoclasts that break down that matrix is necessary to maintain healthy, functional bones"
Can an operational description i.e. a cause why "it is necessary" be provided? What is "it"?

Posted by: morris at January 6th, 2022 7:59 PM
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