Modern Developments in Bone Homeostasis Regulation

Hazem Ahmed^*
*Correspondence: Hazem Ahmed, Department of Neuroscience, Max Rubner Institute, Hermann-Weigmann Street, Kiel, Germany, Email:

Editorial

The adult skeleton has a complex process for maintaining bone homeostasis. The skeletal tissue in humans is constantly undergoing remodelling. Osteoblasts, osteoclasts, and osteocytes-the three primary bones cells-are involved in this remodelling process through the control of molecular signalling pathways. In the process of remodelling bone, osteoclasts remove the distinct zones of bone and osteoblasts replace them with new bone. This allows for the repair of bone micro-injuries and the adaptation of the bone niche for control of mechanical strengths. In order to maintain and create new, healthy bones, osteoblast cells are active in protein synthesis and matrix secretion. Fully differentiated and mature osteoblasts develop into osteocytes and are implanted in the bone matrix after the mineralization of the bone matrix.

Osteocytes and mechanosensory cells serve as bone orchestrators during the remodelling of bone. Numerous regional (growth factors, cytokines, chemokines, etc.) and systemic (oestrogens, etc.) factors work together to maintain bone homeostasis and regulate this remodelling process. Osteocytes work independently to fine-tune bone structure during the bone modelling process, that is, during the stages of bone growth and bone resorption. It's interesting to note that during bone remodelling, these cells function as recyclers to maintain and restore skeletal health. Following an osteoclast-mediated bone resorption cycle, osteoblasts engage the degraded surface of trabecular bone to produce bone matrix and subsequently carry out mineralization. Under typical physiological conditions of bone homeostasis, osteoclastic and osteoblastic actions work in tandem to entirely replace degraded bone with new bone. Osteoporosis, Paget's disease, rheumatoid arthritis (RA), osteoarthritis, and autoimmune arthritis are all examples of bone pathological diseases that result from fluctuations in this homeostatic equilibrium in favour of excessive osteoclast activity. However, osteopetrotic phenomena may result from poor osteoclast differentiation and/or function. However, increased osteoblastic activity results in an osteosclerotic phenotype, while decreased osteoblastic activity causes osteomalacia or rickets. In order to comprehend disease mechanisms and create innovative treatments for bone illnesses, it is crucial to understand the mechanism of bone homeostasis.

The receptor activator of nuclear factor B (NFB) ligand (RANKL), a tumour necrosis factor (TNF) family cytokine, and the macrophage/ monocyte colony-stimulating factor (MCSF) are two essential factors that osteoclast precursor cells derived from haematopoietic stem cells (HSC) nichemonocyte/macrophage lineage cells differentiate into multinucleated giant cells, or osteoclasts. Osteoblasts and stromal cells primarily express MCSF and RANKL, which effectively control the differentiation and operation of osteoclasts. Growth and survival of osteoclast precursor cells depend on M-CSF signalling.

When M-CSF attaches to colony stimulating factor 1 receptor (c-Fms), which is found on osteoclast precursors, it sends signals that help the progenitors survive. When M-CSF binds to its receptor c-Fms, adaptor proteins and cytosolic kinases are recruited, which activates a number of intracellular signals. Additionally, M-CSF activates the essential osteoclastogenesis regulators PI3-kinase, the receptor RANK for RANKL, and other RANK/NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway components. The RANK interacts with its extracellular signal factor RANKL to take on a trimetric configuration. Instead of recruiting adaptor molecules like TNF receptor-associated factors (TRAFs) and Grb2 associated binder (Gab) 2 for signal transduction, the intracellular domain of the RANK trimer, which is expected to lack signalling domains, recruits these molecules. TRAF6 is a crucial adaptor needed for RANK-associated signalling for osteoclastogenesis among the various TRAF proteins that have been linked to RANKL, including TRAF1/2/3/5/6.

Therefore, intracellular RANK signalling via its interaction with RANKL induces recruitment and activation of its adaptor TRAF6, which in turn activates a number of downstream signalling cascades, including mitogenactivated protein kinases (MAPKs) like ERK, p38, and JNK (c-Jun N-terminal kinases) as well as TAK1 activate inhibitory B (IB) kinases (IKKs (also known as protein kinase B). In addition to these two positive regulators of osteoclast differentiation, osteoblasts also express osteoprotegerin (OPG), a secreted member of the TNF receptor superfamily, which is a negative regulator of osteoclast differentiation.

Three important bone cells, osteoclasts, osteoblasts, and osteocytes, regulate the dynamic equilibrium known as bone homeostasis. As long as these cells' activities are properly balanced, net bone mass is maintained, and bone homeostasis is preserved. This equilibrium suggests the existence of molecular mechanisms that closely regulate osteoblast, osteocyte, and osteoclast development as well as their migration to functional sites. In the near future, treating bone illnesses like osteoporosis may offer therapeutic possibilities when senescent cells are targeted [1-5].

Acknowledgement

None.

Conflict of Interests

None.

REFERENCES

1. Aghdasi, B., S.R. Montgomery, M.D. Daubs, and J. C. Wang. "A review of demineralized bone matrices for spinal fusion: The evidence for efficacy." Surgeon 11(2013): 39-48.

Indexed at, Crossref, Google Scholar

2. Ahmed, Tamer A.E., Emma V. Dare, and Max Hincke. "Fibrin: A versatile scaffold for tissue engineering applications." Tissue Eng Part B Rev 14(2008): 199-215.

Indexed at, Crossref, Google Scholar

3. Albanese, Antonino, Maria E. Licata, Bianca Polizzi, and Giuseppina Campisi. "Platelet-rich plasma (PRP) in dental and oral surgery: From the wound healing to bone regeneration." Immun Ageing 10 (2013): 1-10.

Indexed at, Crossref, Google Scholar

4. Alberio, L., O. Safa, Kenneth John Clemetson, C.T. Esmon, and G.L. Dale. "Surface expression and functional characterization of α-granule factor V in human platelets: Effects of ionophore A23187, thrombin, collagen, and convulxin." Am J Hematol 95 (2000): 1694-1702.

Indexed at, Crossref, Google Scholar

5. Alsousou, J., M. Thompson, P. Hulley and K. Willett, et al. "The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: A review of the literature." J Bone Jt Surg 91 (2009): 987-996.

Crossref, Google Scholar