Fluid Flow enhances Osteoclast Production

Cortical bone is detrimental to longitudinal bone growth as it is not capable of interstitial growth. Osteoclasts degrade cortical bone. Degradation of cortical bone in combination with generation of tissue capable of interstitial growth is key to height growth. Thus if fluid flow increase osteoclastgenesis this should be beneficial.

SUPRAPHYSIOLOGICAL LOADING INDUCES OSTEOCYTE-MEDIATED OSTEOCLASTOGENESIS IN A NOVEL IN VITRO MODEL FOR BONE IMPLANT LOOSENING

“We aimed to develop an in vitro model for bone implant loosening, allowing analysis of
biophysical and biological parameters contributing to mechanical instability-induced
osteoclast differentiation and peri-implant bone loss. MLO-Y4-osteocytes were mechanically
stimulated for 1h by fluid shear stress using regimes simulating 1) supraphysiological loading
in the peri-prosthetic interface (2.9+/-2.9Pa, 1Hz, square wave),{This is below the minimum chondregenic range which is about 0.1MPa or 100Pa} 2) physiologic loading in the
cortical bone (0.7+/-0.7Pa, 5Hz, sinusoidal wave), and 3) stress shielding. Cellular
morphological parameters, membrane-bound RANKL expression, gene expression
influencing osteoclast differentiation, nitric oxide release and caspase 3/7-activity were
determined. Either Mouse bone marrow cells were cultured on top of loaded osteocytes or
osteocyte-conditioned medium was added to bone marrow cells. Osteoclast differentiation
was assessed after 6 days. We found that osteocytes subjected to supraphysiological loading
showed similar morphology and caspase 3/7-activity compared to simulated physiological
loading or stress shielding. Supraphysiological stimulation of osteocytes enhanced osteoclast differentiation by 1.9-fold compared to physiological loading when cell-to-cell contact was permitted{this is not a bad thing as degradation of bone could potentially be beneficial for height growh}. In addition, it enhanced the number of osteoclasts using conditioned medium by 1.7-fold, membrane-bound RANKL by 3.3-fold, and nitric oxide production by 3.2-fold. The stimulatory effect of supraphysiological loading on membrane-bound RANKL and nitric oxide production was higher than that achieved by stress shielding. In conclusion, the in vitro model developed recapitulated the catabolic biological situation in the peri-prosthetic interface during instability that is associated with osteoclast differentiation and enhanced RANKL expression. The model thus provides a platform for pre-clinical testing of pharmacological interventions with potential to stop instability-induced bone implant
loosening.”

“[There’s] a specific role for osteocyte communication with osteoclasts “<-Osteoclasts, the cells that break down and reabsorb bone, stem from monocytes and macrophages rather than osteogenic cells.

“The decoy receptor for RANKL, osteoprotegrin (OPG), is released by osteocytes upon
physiological mechanical loading. ”

“Supraphysiological loading had a flow velocity that was 5.6-fold higher, and the wall shear stress rate that was 4.0-fold higher compared to physiological loading”

“Sixty minutes of supraphysiological loading on MLO-Y4 osteocytes did not change the
cell area, cell perimeter or cell feret’s diameter compared to physiological loading or stress
shielding”<-it would be beneficial if it did because it would indicate that the stem cells could possibly change in diameter.

Osteoblasts, Osteoclasts, and Osteocytes: Unveiling Their Intimate-Associated Responses to Applied Orthodontic Forces

“Bone is remodeled and modeled by the concerted activities of 3 cell types—osteoblasts, osteocytes, and osteoclasts. Osteoblasts are the cells that produce bone extracellular matrix and are responsible for its mineralization. Osteoblasts also have endocrine activity through secretion of osteocalcin, which regulates fat and energy metabolism. These cells also control the differentiation and activity of osteoclasts. Osteocytes are osteoblasts that have been incorporated into bone matrix and are cells with extensive dendritic processes through which the cells communicate with other osteocytes and with osteoblasts. Mechanical loading is sensitized by the dendritic processes and transferred to biochemical responses involved in control of osteoblast and osteoclast function. Osteocytes also have endocrine activity by releasing fibroblast growth factor 23, which is involved in phosphate secretion in kidneys. Differentiation of osteoclast mononuclear progenitors to mature multinucleated osteoclasts is regulated by macrophage colony-stimulating factor and receptor activator of NF-κB ligand, expressed by stromal cells in bone marrow or osteoblasts in bone, as well as by osteocytes. The integrated endo- and paracrine control of osteoblasts, osteocytes, and osteoclasts is important for maintaining bone mass and for control of remodeling and modeling processes in bone, including during orthodontic-induced tooth movement.”

“Histologically, the skeleton comprises 2 types of bone tissue: cortical (compact) and trabecular (cancellous) bone. The cortical bone makes up 80% of the volume in the adult skeleton and the trabecular bone makes up the remaining 20%. The cortical bone forms a peripheral shell in all kinds of bone.”

“The vertebrae are most rich in trabecular bone”

“Modeling of the bone is a process that changes the size and shape of bone either by bone resorption without subsequent bone formation or bone formation without previous bone resorption.”

“microcracks in bone and subsequent apoptosis in osteocytes will activate lining cells in
the remodeling process to stimulate osteoclast formation and bone resorption of the microdamaged area. During the resorption process, growth factors in bone are released, which attract and activate osteoblasts to form new bone under a canopy of bone lining cells.”

“. Osteoblasts form a 1 cell layer covering all bone surfaces. One function is to synthesize an extracellular matrix, consisting of type I collagen fibers and several other proteins, and to subsequently mineralize this matrix into bone”

“Osteoclasts are the only cells in nature that can degrade mineralized bone tissue and are important for physiological remodeling and modeling processes”

Natural Height Growth

Cancer, Stem Cells, Regenerative Tissue Engineering, Transdifferentiation

Fluid Flow enhances Osteoclast Production