The Effects of Oscillatory Compression, Static Compression and Electromagnetic Fields on Protein Synthesis Within Articular Cartilage

Abstract

This study found that three types of stimuli are required to keep knee cartilage healthy. These stimuli are:

oscillatory compression,
static compression, and
electromagnetic fields.

By compiling data from clinical studies, the optimal ranges for each type of stimuli were determined. The greatest amount of stimulation in the oscillatory and static compression studies were suggested to occur at 2% strain applied at a frequency of 0.1 Hz and loads of 5-10 MPa applied for four hours. Electromagnetic field stimulation data showed that current densities applied to the cartilage in the range of 13-30 mA/cm2 at a frequency of 100 Hz stimulated the cartilage by 59%. When a leg is immobilized after a break or surgery, cartilage in the knee dies from lack of stimulation. Since it is impossible to regenerate cartilage, joint stiffness results. The optimal ranges found in the study will be used to develop a microprocessor-controlled knee brace that will mimic natural stimulation of cartilage.

Background

Cartilage is located in the knee and is a non-vascular, aneral tissue that provides a low-friction, wear-resistant surface. The function of the cartilage is to distribute and transmit the stresses between the femur and the tibia that are generated by everyday activities such as walking. The components that make up cartilage are:

oscillatory compression,
static compression, and
electromagnetic fields.

These components deteriorate rapidly if they are not stimulated. When a limb is broken or fractured, traditional forms of treatment use immobilization techniques. The immobilization of the limb or joint may last for months, and, during that time, the cartilage and other tissues of the knee die from lack of stimulation. As the cartilage cells die, the smooth surface of the cartilage tissue becomes rough due to the deterioration of the cartilage matrix. This causes friction within the knee joint which can lead to joint stiffness. After the knee is remobilized, it is impossible to completely regenerate the cartilage that has been lost, even after months of physical therapy. Patients often experience a permanent reduction in the range of motion of the knee joint after remobilization due to lack of stimulation during the immobilization period (Oegema).

Cartilage requires nutrients to sustain life and synthesize new cartilage components. These are provided to the extra cellular matrix through stimulation. Because the cartilage cannot be supplied with nutrients through the cardiovascular system, the nutrients must be supplied through the interstitial fluid. Oscillatory and static compression cause the interstitial fluid to flow from the nutrient-rich area, located in the posterior region of the knee, to the nutrient-seeking cartilage matrix. When the cartilage has the nutrients it needs, it produces new cells and thus the cartilage is regenerated (Stark).

Stimulation is measured by the amount of protein synthesis that occurs. Stimulation of cartilage occurs during a compression cycle. A compression cycle has two phases: compression and relaxation. During the compression phase, interstitial fluid flows out of the ECM to the posterior region of the knee joint. The process of interstitial fluid flow is similar to squeezing water from a sponge. During the relaxation phase, the cartilage tissue relaxes and draws the nutrient-rich interstitial fluid back into the ECM. This interstitial fluid provides nutrients to the non-vascular cartilage tissue (ibid).

There are two types of compression, oscillatory and static. Oscillatory compression occurs when the cartilage is compressed under a specific load for a short period of time and then allowed to relax. Everyday activities such as running and walking cause oscillatory compression. Oscillatory compression is cyclic and occurs rapidly with as many as 10 cycles per second (Sah et al.).

Static compression occurs when the cartilage is compressed though loading for a prolonged period of time and then allowed to relax without being recompressed. Static compression occurs in everyday situations such as standing in line. Varying amounts of loading cause a strain to be induced within the cartilage cells. Static compression is measured as a percent strain. The equation for calculating the strain of cartilage tissue for a specified thickness is:

100 x (original thickness - compressed thickness)/original thickness (Hall et al.).

Cartilage is also stimulated by naturally occurring electrical charges created during the compression cycle. When the interstitial fluid is being forced out and drawn back into the ECM during the compression cycle, the friction between the fluid and the solid cartilage components creates a positive electrical charge within the fluid. Different current densities are produced when varying amounts of mechanical loading or compression are applied. The data from the clinical study on electromagnetic fields used electrodes to bombard the cartilage tissue with electromagnetic fields of varying frequencies and current densities. These electromagnetic fields artificially reproduce the electrical charges that occur naturally during a compression cycle (MacGinitie).

Methods

Studies were located using an on-line medical journal cataloging system called MEDLINE. The studies were found at Diehl Hall Biomedical Library and Walter Library at the University of Minnesota.

Results

On the graphs that follow, cartilage stimulation was measured as percent physiological change of stimulated cartilage versus unstimulated cartilage. The physiological changes were reported in the following manner:

If there was more protein synthesis in the stimulated cartilage versus the non-stimulated cartilage, a positive percent physiological change was reported.
If protein synthesis was the same, the percent physiological change was zero.
If there was decreased protein synthesis in the stimulated cartilage compared to non-stimulated cartilage, a negative percent physiological change was reported.

In Figure 1, the oscillatory compression studies show that percent strains between 2% and 5% produce the greatest amounts of stimulation. The highest levels of stimulation, 105% and 96%, occurred at 1.9% strain applied at a frequency of 0.001 Hz and 2.0% strain applied at a frequency of 0.001 Hz, respectively. The lowest level of stimulation was -28% and occurred at a strain of 1.1% applied at a frequency of 1.0 Hz. The trials that tested a frequency of 0.01 Hz applied within a strain range of 0.6% to 4.5% yielded stimulation levels between -2% and 31%. Frequencies of 0.1 Hz applied at strains between 0.7% and 10.38% induced levels of stimulation between -14% and 55%.

In Figure 2, the static compression studies show that all loads of static compression applied within the physiological range (5-15 MPa) for either two hours or four hours produce positive amounts of protein synthesis. The greatest amounts of protein synthesis occurred at loads of 5 and 10 MPa applied for four hours. These two loads stimulated protein synthesis by 100% and 105%, respectively. Loads between 5 and 15 MPa applied for two hours also produced stimulation, but at rates much lower than those of the four hour trials. Ranges of stimulation for the two hour trials ranged from 10% stimulation (under a load of 10 MPa) to 25% stimulation (under a load of 5 MPa). Loads that were applied to the cartilage outside of the upward end of the physiological range (loads greater than 15 MPa) led to degradation of protein synthesis. The greatest amount of negative stimulation occurred at a load of 50 MPa applied for a duration of two hours.

As seen in Figure 3, the results for the electromagnetic field stimulation study were varied. Amounts of stimulation ranged from a low of -27% obtained with a current density of 10 mA/cm2 applied at a frequency of 10 Hz to a high of 59% obtained with a current density of 24 mA/cm2 applied at a frequency of 100 Hz. The trials that used a frequency of 1 Hz produced the least amounts of stimulation of all the frequencies tested. All of the 1 Hz stimulation rates were below 14%. Protein synthesis rates of the 1 Hz trials were closest to the amounts of protein synthesis that took place in the non-stimulated cartilage. The trials conducted with frequencies of 10 KHz also produced low amounts of stimulation. Stimulation levels were between -4.5% (when a current density of 10 mA/cm2 was applied) and 16% (when a current density of 20 mA/cm2 was applied). Frequencies of 1 KHz produced the second highest levels of stimulation for the study. Stimulation rates of the 1 KHz trials were between 13% (obtained using a current density of 8 mA/cm2) and 39% (obtained using a current density of 10 mA/cm2). Trials conducted using a frequency of 10 Hz produced varied data. It produced the second highest amount of stimulation and the highest amount of negative stimulation in the study. Stimulation of -27% was found to occur at a current density of 10 mA/cm2. However, stimulation of 39% was produced using a current density of 30 mA/cm2. The results that produced the greatest amounts of stimulation occurred with the 100 Hz trials. The highest amounts of stimulation occurred for current densities between 13 and 30 mA/cm2. The highest amount of stimulation in the study occurred at a current density of 24 mA/cm2 applied at a frequency of 100 Hz. Current densities between 13 and 30 mA/cm2 all stimulated the cartilage at or above 12%.

Conclusion

From the data on oscillatory compression, it can be concluded that a frequency of 0.001 Hz applied around a 2% strain seems to produce the greatest amount of stimulation. For the study on static compression, the data shows that a load of 5-10 MPa applied for a duration of four hours seems to produce the greatest physiological benefits. It can be concluded that optimal current densities are between 13 and 30 mA/cm2 applied at a frequency of 100 Hz. This range of densities and frequencies can increase protein synthesis rates by up to 59%.

Discussion

To obtain specific, controlled data that can positively identify how different variables affect stimulation of cartilage, a study needs to be conducted that uses similar cartilage samples and tests only one variable at a time. The study needs to test the effects of oscillatory compression through independent variations in frequencies and strains. Developing a procedure to test the cartilage in this way would yield better information about which stimuli has the optimal effect on cartilage stimulation. It would also be useful to develop a test in which the effects of static compression could be tested through independent variations in duration and load. Developing a procedure to test the cartilage in this way would also yield better information about which stimuli has the optimal effect on cartilage stimulation.

The studies that tested compression have important applications in the micro-processor controlled knee brace. Since the brace will be computer controlled, exercises can be programmed in the computer of the brace. Information learned from this study will aid in the development of the exercises to be programmed into the computer. Exercises that use minute controlled movements of the knee joint can be used to achieve duration, loads, and strain levels of oscillatory and static compression that fall in the ranges this study suggests. These controlled exercises will have the potential to minimize cell death within the cartilage during the time the brace is worn. Thus the recovery time following joint trauma will hopefully be shorter and more successful .

By applying a pulsed electromagnetic field at a frequency of 100 Hz with a current density between 13 and 30 mA/cm2 to a medical apparatus (i.e., a micro-processor controlled knee brace), the cartilage in the knee could be stimulated by electrodes while motionless. The cartilage could thus be stimulated to maintain normal biosynthetic functions after surgery when the knee is immobilized. This type of stimulation would be desirable as large movements of the knee joint (the only traditional way to stimulate the cartilage) disturbs the fragile environment of the knee tissues that are damage prone following surgery. However, more stimulation may not always be better. It must be determined if excessively high amounts of stimulation are detrimental to cartilage health.

Works Cited

Chen, A.C., Johnson, E.B., Nagrampa, J.P., Sheeter, L.M. and Sah, R.L. The effect of static loading on proteoglycan biosynthesis by chondrocytes transplanted to articular cartilage in vitro. 43rd Annual Meeting, Orthopaedic Research Society . 201-34, 1997 Feb.

Hall, A.C., Urban, J.P.G. and Gehl, K.A. The effects of hydrostatic pressure on matrix synthesis in articular cartilage. Journal of Orthopaedic Research. 9(1): 1-10, 1991.

Kim, Young-Jo, Sah, Robert L.Y., Grodzinsky, Alan J., Plass, Anna H.K. and Sandy, John D. Mechanical regulation of cartilage biosynthetic behavior: physical stimuli. Archives of Biochemistry and Biophysics . 311(1): 1-12, 1994 May.

MacGinitie, L.A., Gluzband, Y.A. and Grodzinsky, A.J. Electric field stimulation can increase protein synthesis in articular cartilage explants. Journal of Orthopaedic Research . 12(1): 151-160, 1994.

Oegema, Theodore R. Jr. Ph.D. Lecture. M.D.-Ph.D. Seminar. City of St. Paul. Institute for Sports Medicine, 25 June 1997.

Sah, Robert L.-Y., Kim, Young-Jo, Doong, Joe-Yuan H., Grodzinsky, Alan J., Plass, Ann H.K. and Sandy, John D. Biosynthetic response of cartilage explants to dynamic compression. Journal of Orthopaedic Research. 7(5): 619-636, 1989.

Stark, John G. M.D. Lecture. City of Minneapolis. IZEX Technologies, 11 July 1997.