Why don't osteoblasts make us taller?

In our discussion on water and height, we went over the differences between chondrocytes and osteoblasts and tried to determine why chondrocytes can cause interstitial growth whereas osteoblasts cannot.  Both chondrocytes and osteoblasts secret ECM(osteoblasts secret Type I collagen) but cartilage is far more hydrophillic(water loving).  Since cartilage is more hydrophillic it is more prone to hypertrophy thus that could be a key to why chondrocytes are a key to growing taller.  Do osteoblasts undergo hypertrophy and if they do then why don't they make you taller like chondrocytes?  Osteoblasts also undergo apoptosis but maybe water release from apoptotic chondrocytes can help you grow taller.

Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways.

"Insulin dependent diabetes mellitus (IDDM; type I) is a chronic disease stemming from little or no insulin production and elevated blood glucose levels. IDDM is associated with osteoporosis and increased fracture rates. The mechanisms underlying IDDM associated bone loss are not known. Previously we demonstrated that osteoblasts exhibit a response to acute (1 and 24 h) hyperglycemia and hyperosmolality[so there is a high number of solute in the body so osteoblasts release water and shrink]. Here we examined the influence of chronic hyperglycemia (30 mM) and its associated hyperosmolality on osteoblast phenotype. Our findings demonstrate that osteoblasts respond to chronic hyperglycemia through modulated gene expression. Specifically, chronic hyperglycemia increases alkaline phosphatase activity and expression and decreases osteocalcin, MMP-13, VEGF and GAPDH expression. Of these genes, only MMP-13 mRNA levels exhibit a similar suppression in response to hyperosmotic conditions[MMP-13 degrades extracellular matrix, so hyperosmotic conditions suppress degradation of the extracellular matrix] (mannitol treatment). Acute hyperglycemia for a 48-h period was also capable of inducing alkaline phosphatase and suppressing osteocalcin, MMP-13, VEGF, and GAPDH expression in differentiated osteoblasts. This suggests that acute responses in differentiated cells are maintained chronically. In addition, hyperglycemic and hyperosmotic conditions increased PPARgamma2 expression[PPARgamma is usually associated with increased adipocyte differentiation and reduced osteoblast differentiation], although this increase reached significance only in 21 days chronic glucose treated cultures. Given that osteocalcin is suppressed and PPARgamma2 expression is increased in type I diabetic mouse model bones, these findings suggest that diabetes-associated hyperglycemia may modulate osteoblast gene expression, function and bone formation and thereby contribute to type I diabetic bone loss."

So, hyperosmotic conditions are catabolic to bone cells. So osteoblasts do respond to water much like chondrocytes.

"increased expression of PPARγ2, aP2 and resistin in streptozotocin-induced diabetic mice corresponded with increased adipocyte maturation and suggested the possibility that IDDM may also affect lineage selection of mesenchymal stem cells, leading to adipocyte rather than osteoblast maturation."

"cells can also respond to hyperglycemia through an osmotic response. Because osteoblasts express glucose transporters, GLUT-1 and -3, with low K_m (1–2 mM and <1 mM, respectively), glucose transport is maximal at euglycemic[normal blood glucose levels] state (glucose concentration of 3–5.5 mM) so an increase in extracellular glucose could be an osmotic stress."  Since cells are transporting less glucose there is more glucose outside a cell therefore water leaves the cell to restore concentration to normal.

"During osmoadaptation to extracellular hyperosmotic conditions, virtually all cells undergo a volume change and shrink"<-therefore osteoblasts should be capable of undergoing hypertrophy as well.

"Osteoblast morphology and number does not change under chronic hyperglycemia"<-remember hyperglycemia causes hyperosmolarity as well.  So hyperosmolarity does not cause osteoblast hypertrophy(which would be a part of morphology).  So even though water is leaving the cell, osteoblasts do not stay shrunken in size.

"During this period osteoblasts undergo immediate volumetric changes (cell shrinking) induced by hyperglycemia-associated hyperosmolality"<-Hypertonic means water leaving the cell so it makes sense for cells to shrink

So osteoblasts are osmotically sensitive like chondrocytes.  Do osteoblasts swell(hypertrophy) in response to hyposmotic(water enters the cell) solutions?

Regulation of cell volume and intracellular pH in hyposmotically swollen rat osteosarcoma cells.

"The maintenance of cell volume involves transduction of a volume-sensing signal into effectors of volume-regulatory transporters. After exposure to anisotonic conditions, cells undergo compensatory volume changes that are mediated by active transport and passive movement of ions and solutes. Intracellular pH (pHi) homeostasis may be compromised during these processes. We have studied pHi and some of the signal transduction mechanisms involved in the regulatory volume decrease (RVD) that occurs after exposure to hypoosmolar conditions in rat osteosarcoma cells, ROS 17/2.8. Cells were loaded with BCECF; pHi and cell volume were estimated by dual excitation ratio fluorimetry. Swelling of cells in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffered hypotonic medium induced a rapid cell swelling followed by an incomplete RVD of approximately 30% in suspended (i.e., round) cells and approximately 60% in attached (i.e., spread) cells that was independent of subpassage number[so osteoblast cells did cell and the swelling did not return to normal after time as shown by the incomplete regulatory volume decrease]. RVD was inhibited by ouabain, valinomycin, and high external [K+], all of which should reduce the cell membrane electrochemical gradient for K+. Inhibition of RVD was induced also by decreasing intracellular [Ca2+] with BAPTA-AM and by depletion of Cl-, indicating the role of calcium-regulated K+ and Cl- efflux during RVD. Depolymerization of actin filaments by cytochalasin D prolonged the RVD three-fold and nonspecific activation of GTP-binding proteins up-regulated RVD. In attached cells the hypoosmolar-induced swelling caused a large reduction in pHi (approximately 0.7 units), which was sustained as long as cells were in hypoosmotic medium. The reduction of pHi induced by cell swelling was inhibited by Na(+)-free extracellular medium, ouabain, the tyrosine kinase inhibitor genistein, and to a lesser extent by Cl(-)-free medium. However, amiloride failed to inhibit the hypoosmolar-induced reduction of pHi. Collectively these data indicate that RVD of ROS 17/2.8 cells in HEPES-buffered medium is dependent on conductive efflux of K+ and Cl- that is regulated by cell shape, actin, and GTP-binding proteins. The sustained inhibition of pHi homeostasis induced by cell swelling may reflect the existence of cell volume sensing mechanisms that operate through tyrosine kinases to regulate pHi."


It could be a location issue that chondrocytes are in a better position to increase height than osteoblasts.  However, there are osteoblasts at the surface of the bone with potential for hypertrophy and the ability to secrete extracellular matrix.  However, key components to chondrocyte hypertrophy may not be due to osmotic swelling and may be due to other factors.  It could be these other forms of hypertrophy that are responsible for height growth. 

Since cartilage is hydrophillic, chondrocytes are a lot better at manipulating water levels since it can store water in it's ECM.  Osteoblasts do not have water stored in it's ECM.  Osmotic lysis is more likely to occur in osteoblasts than chondrocytes as chondrocytes have the water storage ability of the cartilage.  Since chondrocytes do have water stored in the ECM, they can better orchestrate the osmotic lysis of the cells thus resulting in an explosion pushing the bone apart.

Hyperosmotic conditions were found to result in more chondrocyte apoptosis.  Water leaving the cell resulted in apoptosis rather than water flooding into the chondrocyte.  During terminal differentiation, cartilage is absorbed leading to less water outside the cell therefore chondrocytes release water to result in osmotic balance this results in chondrocyte apoptosis.  This response did not seem to occur in osteoblast cells which only exprienced decreased expression of MMP-13 and increased levels of PPARgamma2 in response to a hyperosmotic environment like those experienced by chondrocytes who just had their ECM degraded.

There is evidence that there is an active role of chondrocyte apoptosis in endochondral ossification and that active role may play a role in how physically growth plates make you taller.  Other cells do have the ability to influence body shape for example you could have swollen skin.  Osteoblasts have the ability to influence shape too but only by secreting new matrix beneath the periosteum.  This however does not involve hypertrophy or apoptosis but is only the result of matrix secretion.

Therefore, matrix secretion may only be able to cause apopsitional growth but hypertrophy and apoptosis may be needed for interstitial growth.

Growth plate chondrocytes have to do something else besides proliferate, divide and secrete ECM to make us taller.  Lots of cells perform those functions and don't make us taller.  There needs to be a force generated pushing the bone apart from within to make room for new bone.  Choreographed chondrocyte apoptosis has the ability to do that like a string of dynamite.  Osteoclasts can degrade ECM all at once like triggers resulting in chondrocytes going off at once resulting in a big "explosive" force.

If the force isn't big enough like isolated osteoblast apoptosis you won't grow taller.