Table 1. Mechanical stimulations on growth plate chondrocytes.
Year | Reference | Subject | Samples | Experiment type | Tools | Type of stress | Parameters | Brief results [relative to control (or sham) group] | Findings |
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1993 | Alberty et al. [30] | New Zealand white rabbits 5–6 weeks | Left distal femoral physis | in-vivo | External fixator | Static compression |
d = 0.5 mm/day (day ≤ 7 days) d = 3.5 mm (day ≥ 8 days) t = 3–21 days |
The height of proliferative and hypertrophic zones: ↓ The height of resting zone: - The orientation of chondrocyte columns: distorted The number of proliferating chondrocytes:↓ |
1. Static compression suppresses growth plate proliferative activity and change growth plate morphology. 2. The role of static tension on bone growth is not clear. |
Static tension |
d = 0.7 mm/day, t = 3–21 days |
The Hight of proliferative and hypertrophic zones: ↑ The number of proliferating chondrocytes: - |
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2001 | Robling et al. [34] | Male Sprague Dawley rat | Ulna | in-vivo | Compression device | Static compression |
F = 17 N t = 10 min/day (days 1–5, 8–12) |
Length of ulna: ↓ 4% | 1. Peak load magnitude affects the growth suppression regardless of the type of compression and average load magnitude. 2. Thicker distal growth plate and accumulation of hypertrophic cell lacunae are related with growth suppression accumulation of hypertrophic cell lacunae are related with growth suppression. |
F = 8.5 N t = 10 min/day (days 1–5, 8–12) |
Length of ulna: ↓ 2% | ||||||||
Dynamic compression |
F = 17 N f = 2 Hz t = 10 min/day (days 1–5, 8–12) |
Length of ulna: ↓ 4% | |||||||
2002 | Wang and Mao [36] | New Zealand white rabbits 6 weeks | Cranial base growth plate | in-vivo | Mechanical testing equipment connected to maxillary central incisors | Static tension |
F = 2 N t = 20 minutes/day (12 days) |
Height of growth plate: ↑ 16% Height of proliferation zone: ↑ 117% The number of proliferative chondrocytes: - |
1. Dynamic tension promotes chondral growth. |
Dynamic tension |
F = 2 N f = 1 Hz t = 20 minutes/day (12 days) |
Height of growth plate: ↑ 54% Height of proliferation zone: ↑ 193% The number of proliferative chondrocytes: ↑ 65% |
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2002 | Stokes et al.[13] | Sprague Dawley rat | Caudal vertebra | in-vivo | External fixator | Static compression |
F = 60% of body weight (~ 0.736 N) t = 4 weeks |
Growth rate: ↓ 48% Height of hypertrophic zone: ↓ 13% Mean chondrocyte height: ↓ 15% |
1. The effect of static compression is greater than static tension in bone growth. 2. The change in height of hypertrophic chondrocytes is related to growth rate. |
Static tension |
F = 60% of body weight (~ 0.736 N) t = 4 weeks |
Growth rate: ↑ 13% Height of hypertrophic zone:- Mean chondrocyte height: - |
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2006 | Akyuz et al. [32] | Sprague Dawley rat | Caudal vertebra | in-vivo | External fixator | Static compression |
F = 55% of body weight t = 3 weeks Asymmetric load |
Average wedge deformity: 10.3 ± 3.7° (sham / control group: 1.1 ± 20°/ 0.0 ± 1.0°) Longitudinal growth: 0.46 ± 0.19 mm (concavity) / 0.83 ± 0.32 mm (convexity) |
1. Dynamic compression has greater effects on the growth regulation. |
Dynamic compression |
F = 55% of body weight f = 1.0 Hz t = 3 weeks Asymmetric load |
Average wedge deformity: 15.2 ± 6.4° Longitudinal growth: 0.34 ± 0.23 mm (concavity) / 0.86 ± 0.23 mm (convexity) |
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2007 | Stokes et al. [31] | Rat, 38 days Rabbit, 41 days Cattle, 48 days | Proximal tibia (Rat, cattle and rabbit) Caudal vertebra (Rat and cattle) | in-vivo | External fixator | Static compression |
P = 0.1 MPa/0.2 MPa t = 7 days |
Growth rate: ↓ | 1. The height of hypertrophic chondrocytes have a greater effect on growth rate than the number of proliferative chondrocytes. |
Static tension |
P = 0.1 MPa t = 7 days |
Growth rate: ↑ | |||||||
2008 | Ueki et al. [25] | Male Wistar strain rat 4 weeks | Chondrocytes from rib growth plate | in-vitro | 2D cell stretcher | Dynamic tension (2D) |
P = 2 kPa f = 0.03 Hz t = 12 or 24 hours |
Chondrocyte proliferation: - Collagen and proteoglycan syntheses: - |
1. Chondrocyte metabolism improved due to increased frequency of tension. |
P = 2 kPa f = 0.5 Hz t = 12 or 24 hours |
Chondrocyte proliferation: ↑ Collagen and proteoglycan syntheses: ↑ |
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P = 2 kPa f = 2.5 Hz t = 12 or 24 hours |
Chondrocyte proliferation: ↑ Collagen and proteoglycan syntheses:↑ |
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2009 | Cancel et al. [16] | Male Sprague Dawley rat | 7th Caudal vertebra (Cd7) | in-vivo | External fixator | Static compression |
P = 0.2 MPa t = 2 weeks |
Longitudinal growth rate: ↓ 28% Growth plate thickness: ↓ 25% Amount of MMP-3 expression: ↑ Type II and X collagen: ↓ |
1. The growth of caudal vertebrae was suppressed by 2-week static compression. |
2011 | Valteau et al. [17] | Male Sprague Dawley rat | 7th Caudal vertebra (Cd7) | in-vivo | External fixator with pneumatic loading system | Static compression |
P = 0.2 MPa t = 2 weeks |
Growth rate: ↓ 21% Growth plate height: ↓ 20% Hypertrophic chondrocyte height: ↓ 25% The number of proliferative chondrocytes per column: ↓ 32% | 1. Both static and dynamic compression modulate bone growth effectively. 2. Dynamic compression is less harmful on growth plate morphology than static compression. |
Dynamic compression |
P = 0.2 ± 0.06 MPa f = 0.1 Hz t = 2 weeks |
Growth rate: ↓ 21% Growth plate height: ↓ 11% Hypertrophic chondrocyte height: ↓ 15% The number of proliferative chondrocytes per column: ↓ 19% |
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2011 | Sergerie et al. [23] | Swine 4 weeks | Distal ulnae (cylindrical explant, D = 6 mm, h = 3.04 ± 0.54 mm) | ex-vivo | Compression device with parallel plate | Static compression |
ε = 10% t = 2 days |
Chondrocyte column: structure is reserved Aggrecan, type II collagen, type X collagen, and MMP13:↓ |
1. Growth plate behaves differently depending on the type of compressive stress. 2. Dynamic compression increases the expression of extracellular matrix components. |
Dynamic compression |
ε = 7 and 13% f = 0.1 Hz t = 2 days |
Chondrocyte column: structure is distorted Aggrecan and type II collagen:↑ |
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2014 | Menard et al. [35] | Male Sprague Dawley rat 4 weeks | 7th Caudal vertebra (Cd7) | in-vivo | External fixator with pneumatic loading system | Dynamic compression |
P = 0.2 ± 0.06 MPa f = 1.0 Hz t = 15 days |
Growth rate: ↓ 16% Growth plate height: ↓ 17% Hypertrophic chondrocyte height: ↓ 14% The number of proliferative chondrocytes per column: ↓15% |
1. Increase in both magnitude and frequency of the stress destroys the integrity of growth plate. |
P = 0.2 ± 0.2 MPa f = 0.1 Hz t = 15 days |
Growth rate: ↓ 17% Growth plate height: ↓ 8% Hypertrophic chondrocyte height: ↓ 11% The number of proliferative chondrocytes per column: ↓ 13% |
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P = 0.2 ± 0.14 MPa f = 1.0 Hz t = 15 days |
Tissues were damaged. | ||||||||
2015 | Kaviani et al. [24] | Swine 4 weeks | Distal ulnae (cylindrical explant) D = 6 mm h = 9 mm | ex-vivo | Compression device with parallel plates | Static compression | P = 0.1 MPa / t = 12 hours | High stress:↓ viability of chondrocytes High frequency:↓ viability of chondrocytes Long loading time: ↓ viability of chondrocytes |
1. Chondrocyte viability significantly decreases under the static compression with long loading time. 2. Proliferative and hypertrophic chondrocytes are susceptible to the stress. |
P = 0.2 MPa / t = 12 hours | |||||||||
P = 0.1 MPa / t = 24 hours | |||||||||
Dynamic compression | P = 0.1 ± 0.03 MPa /f = 0.1 Hz t = 12 hour | ||||||||
P = 0.2 ± 0.06 MPa /f = 0.1 Hz t = 12 hour | |||||||||
P = 1.0 ± 0.03 MPa /f = 0.1 Hz t = 24 hour | |||||||||
P = 0.1 ± 0.03 MPa /f = 0.1 Hz t = 12 hour | |||||||||
P = 0.1 ± 0.1 MPa /f = 0.1 Hz t = 12 hour | |||||||||
2017 | Zimmermann et al. [20] | Male Sprague Dawley rat 27–30 days | Growth plate explants from tibia | ex-vivo | Compression device with parallel plate | Static compression |
P = 0.2 MPa t = 2 hours |
Hypertrophic chondrocytes compressed more in lateral direction than axial direction | 1. Axial strains of hypertrophic chondrocytes are similar in all stress conditions. 2. Volumetric strains of cells decrease when the frequency becomes higher. |
Dynamic compression |
P = 0.2 ± 0.06 MPa f = 0.1 Hz t = 2 hours |
Hypertrophic chondrocytes maintained their shape under dynamic compression | |||||||
P = 0.2 ± 0.06 MPa f = 1.0 Hz t = 2 hours |
Hypertrophic chondrocytes maintained their shape under dynamic compression | ||||||||
2017 | Sun et al. [27] | Human (children with thumb duplication) | Chondrocytes from the growth plate of multi-fingered phalange | in-vitro | 2D cell stretcher | Dynamic 2D stretching |
ε= 0.2% f = 0.5 Hz t = 6 hours |
Type 2 collagen, Type 10 collagen, and PTHrP: ↑ | 1. Proper amount of stretch promotes proliferation and differentiation of chondrocytes. 2. Excessive amount of stretch inhibits proliferation and differentiation of chondrocytes. 3. Excessive amount of stretch may induce cell death. |
ε= 0.4% f = 0.5 Hz t = 6 hours |
Type 2 collagen, Type 10 collagen, and PTHrP: ↓ |