Advertisement
Research Article| Volume 11, ISSUE 5, P146-155, October 2022

Dynamic loading stimulates mandibular condyle remodeling

Published:September 22, 2022DOI:https://doi.org/10.1016/j.ejwf.2022.08.002

      Highlights

      • Similar to the bone, condylar cartilage responds and adapts to dynamic loading in vivo.
      • High frequency, low-magnitude load applied through the mandibular molars increases mesenchymal cell proliferation and chondrogenic differentiation in the condylar cartilage.
      • Dynamic loading stimulates the expression of both chondrogenic and osteogenic markers in condyles.
      • Dynamic loading increases endochondral bone formation and bone density of the condylar process.
      • In response to dynamic load the condylar process lengths.
      • This effect might help regenerate condylar cartilage and enhance or facilitate the correction of mandibular deficiencies when combined with orthopedic appliances.

      ABSTRACT

      Background

      We and others have reported that low-magnitude high-frequency dynamic loading has an osteogenic effect on alveolar bone. Since chondrocytes and osteoblasts originate from the same progenitor cells, we reasoned that dynamic loading may stimulate a similar response in chondrocytes. A stimulating effect could be beneficial for patients with damaged condylar cartilage or mandibular deficiency.

      Methods

      Studies were conducted on growing Sprague-Dawley rats divided into three groups: control, static load, and dynamic load. The dynamic load group received a dynamic load on the lower right molars 5 minutes per day with a 0.3 g acceleration and peak strain of 30 με registered by accelerometer and strain gauge. The static load group received an equivalent magnitude of static force (30 με). The control group did not receive any treatment. Samples were collected at days 0, 28, and 56 for reverse transcriptase polymerase chain reaction analysis, microcomputed tomography, and histology and fluorescent microscopy analysis.

      Results

      Our experiments showed that dynamic loading had a striking effect on condylar cartilage, increasing the proliferation and differentiation of mesenchymal cells into chondrocytes, and promoting chondrocyte maturation. This effect was accompanied by increased endochondral bone formation resulting in lengthening of the condylar process.

      Conclusions

      Low-magnitude, high-frequency dynamic loading can have a positive effect on condylar cartilage and endochondral bone formation in vivo. This effect has the potential to be used as a treatment for regenerating condylar cartilage and to enhance the effect of orthopedic appliances on mandibular growth.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the World Federation of Orthodontists
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Grodzinsky AJ
        • Levenston ME
        • Jin M
        • Frank EH
        Cartilage tissue remodeling in response to mechanical forces.
        Annu Rev Biomed Eng. 2000; 2: 691-713
        • Mizuno E
        • Wakimoto Y
        • Nomura M
        • et al.
        Effects of different exercises on the growth plate in young growing mice.
        Biomed Res. 2018; 29 (–938X): 0970
        • Villemure I
        • Stokes IA.
        Growth plate mechanics and mechanobiology. A survey of present understanding.
        J Biomech. 2009; 42: 1793-1803
        • Solem RC
        • Eames BF
        • Tokita M
        • Schneider RA.
        Mesenchymal and mechanical mechanisms of secondary cartilage induction.
        Dev Biol. 2011; 356: 28-39
        • Mérida Velasco JR
        • Rodríguez Vázquez JF
        • De la Cuadra Blanco C
        • Campos López R
        • Sánchez M
        • Mérida Velasco JA
        Development of the mandibular condylar cartilage in human specimens of 10–15 weeks' gestation.
        J Anat. 2009; 214: 56-64
        • Delatte M
        • Von den Hoff JW
        • Van Rheden REM
        • Kuijpers-Jagtman AM.
        Primary and secondary cartilages of the neonatal rat: the femoral head and the mandibular condyle.
        Eur J Oral Sci. 2004; 112: 156-162
        • Shen G
        • Darendeliler MA.
        The adaptive remodeling of condylar cartilage—a transition from chondrogenesis to osteogenesis.
        J Dent Res. 2005; 84: 691-699
        • Baume LJ
        • Derichsweiler H.
        Response of condylar growth cartilage to induced stresses.
        Science. 1961; 134: 53-54
        • Moss ML
        • Salentijn L.
        The primary role of functional matrices in facial growth.
        Am J Orthod. 1969; 55: 566-577
        • Moss ML
        • Salentijn L.
        The capsular matrix.
        Am J Orthod. 1969; 56: 474-490
        • Enlow DH
        • Harris DB.
        A study of the postnatal growth of the human mandible.
        Am J Orthod. 1964; 50: 25-50
        • Utreja A
        • Dyment NA
        • Yadav S
        • et al.
        Cell and matrix response of temporomandibular cartilage to mechanical loading.
        Osteoarthritis Cartilage. 2016; 24: 335-344
        • Kaul R
        • O'Brien MH
        • Dutra E
        • Lima A
        • Utreja A
        • Yadav S.
        The effect of altered loading on mandibular condylar cartilage.
        PLoS One. 2016; 11e0160121
        • Teramoto M
        • Kaneko S
        • Shibata S
        • Yanagishita M
        • Soma K.
        Effect of compressive forces on extracellular matrix in rat mandibular condylar cartilage.
        J Bone Miner Metab. 2003; 21: 276-286
        • Kuroda S
        • Tanimoto K
        • Izawa T
        • Fujihara S
        • Koolstra JH
        • Tanaka E.
        Biomechanical and biochemical characteristics of the mandibular condylar cartilage.
        Osteoarthritis Cartilage. 2009; 17: 1408-1415
        • Bouvier M
        • Hylander WL.
        The effect of dietary consistency on gross and histologic morphology in the craniofacial region of young rats.
        Am J Anat. 1984; 170: 117-126
        • Hinton RJ
        • Carlson DS.
        Response of the mandibular joint to loss of incisal function in the rat.
        Acta Anat (Basel). 1986; 125: 145-151
        • Turner CH
        • Forwood MR
        • Rho JY
        • Yoshikawa T.
        Mechanical loading thresholds for lamellar and woven bone formation.
        J Bone Miner Res. 1994; 9: 87-97
        • Oxlund BS
        • Ørtoft G
        • Andreassen TT
        • Oxlund H.
        Low-intensity, high-frequency vibration appears to prevent the decrease in strength of the femur and tibia associated with ovariectomy of adult rats.
        Bone. 2003; 32: 69-77
        • Rubin C
        • Turner AS
        • Bain S
        • Mallinckrodt C
        • McLeod K
        Anabolism. Low mechanical signals strengthen long bones.
        Nature. 2001; 412: 603-604
        • Garman R
        • Gaudette G
        • Donahue LR
        • Rubin C
        • Judex S.
        Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation.
        J Orthop Res. 2007; 25: 732-740
        • Rubin CT
        • Lanyon LE.
        Regulation of bone mass by mechanical strain magnitude.
        Calcif Tissue Int. 1985; 37: 411-417
        • Li Y
        • Frank EH
        • Wang Y
        • Chubinskaya S
        • Huang HH
        • Grodzinsky AJ.
        Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, tumor necrosis factor-α and interleukin-6, but accentuates degradation above a strain threshold.
        Osteoarthritis Cartilage. 2013; 21: 1933-1941
        • Frost HM.
        Mechanical determinants of bone modeling.
        Metab Bone Dis Relat Res. 1982; 4: 217-229
        • Tägil M
        • Aspenberg P.
        Cartilage induction by controlled mechanical stimulation in vivo.
        J Orthop Res. 1999; 17: 200-204
        • von Stengel S
        • Kemmler W
        • Engelke K
        • Kalender WA.
        Effects of whole body vibration on bone mineral density and falls: results of the randomized controlled ELVIS study with postmenopausal women.
        Osteoporos Int. 2011; 22: 317-325
        • Zhou Y
        • Guan X
        • Liu T
        • et al.
        Whole body vibration improves osseointegration by up-regulating osteoblastic activity but down-regulating osteoblast-mediated osteoclastogenesis via ERK1/2 pathway.
        Bone. 2015; 71: 17-24
        • Alikhani M
        • Khoo E
        • Alyami B
        • et al.
        Osteogenic effect of high-frequency acceleration on alveolar bone.
        J Dent Res. 2012; 91: 413-419
        • Alikhani M
        • Lopez JA
        • Alabdullah H
        • et al.
        High-Frequency Acceleration:therapeutic Tool to Preserve Bone following Tooth Extractions.
        J Dent Res. 2016; 95: 311-318
        • Goldring MB
        • Tsuchimochi K
        • Ijiri K.
        The control of chondrogenesis.
        J Cell Biochem. 2006; 97: 33-44
        • Teixeira CC
        • Khoo E
        • Tran J
        • et al.
        Cytokine expression and accelerated tooth movement.
        J Dent Res. 2010; 89: 1135-1141
        • Sobue T
        • Yeh WC
        • Chhibber A
        • et al.
        Murine TMJ loading causes increased proliferation and chondrocyte maturation.
        J Dent Res. 2011; 90: 512-516
        • Pirttiniemi P
        • Kantomaa T
        • Sorsa T.
        Effect of decreased loading on the metabolic activity of the mandibular condylar cartilage in the rat.
        Eur J Orthod. 2004; 26: 1-5
        • Li Z
        • Kupcsik L
        • Yao SJ
        • Alini M
        • Stoddart MJ.
        Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-beta pathway.
        J Cell Mol Med. 2010; 14: 1338-1346
        • Trepczik B
        • Lienau J
        • Schell H
        • et al.
        Endochondral ossification in vitro is influenced by mechanical bending.
        Bone. 2007; 40: 597-603
        • Smith DM
        • McLachlan KR
        • McCall Jr., WD
        A numerical model of temporomandibular joint loading.
        J Dent Res. 1986; 65: 1046-1052
        • Koolstra JH
        • van Eijden TM.
        The jaw open-close movements predicted by biomechanical modelling.
        J Biomech. 1997; 30: 943-950
        • Ikeda Y
        • Yonemitsu I
        • Takei M
        • Shibata S
        • Ono T.
        Mechanical loading leads to osteoarthritis-like changes in the hypofunctional temporomandibular joint in rats.
        Arch Oral Biol. 2014; 59: 1368-1376
        • Tanaka E
        • Koolstra JH.
        Biomechanics of the temporomandibular joint.
        J Dent Res. 2008; 87: 989-991
        • Walker CG
        • Ito Y
        • Dangaria S
        • Luan X
        • Diekwisch TG.
        RANKL, osteopontin, and osteoclast homeostasis in a hyperocclusion mouse model.
        Eur J Oral Sci. 2008; 116: 312-318
        • Prisby RD
        • Lafage-Proust MH
        • Malaval L
        • Belli A
        • Vico L.
        Effects of whole body vibration on the skeleton and other organ systems in man and animal models: what we know and what we need to know.
        Ageing Res Rev. 2008; 7: 319-329
        • Sriram D
        • Jones A
        • Alatli-Burt I
        • Darendeliler MA.
        Effects of mechanical stimuli on adaptive remodeling of condylar cartilage.
        J Dent Res. 2009; 88: 466-470
        • Fujita T
        • Hayashi H
        • Shirakura M
        • et al.
        Regeneration of condyle with a functional appliance.
        J Dent Res. 2013; 92: 322-328
        • Wysocki A
        • Butler M
        • Shamliyan T
        • Kane RL.
        Whole-body vibration therapy for osteoporosis: state of the science.
        Ann Intern Med. 2011; 155: 680-686
        • Totosy de Zepetnek JO
        • Giangregorio LM
        • Craven BC.
        Whole-body vibration as potential intervention for people with low bone mineral density and osteoporosis: a review.
        J Rehabil Res Dev. 2009; 46: 529-542
        • Xie L
        • Jacobson JM
        • Choi ES
        • et al.
        Low-level mechanical vibrations can influence bone resorption and bone formation in the growing skeleton.
        Bone. 2006; 39: 1059-1066
        • Yang P
        • Jia B
        • Ding C
        • Wang Z
        • Qian A
        • Shang P.
        Whole-body vibration effects on bone before and after hind-limb unloading in rats.
        Aviat Space Environ Med. 2009; 80: 88-93
        • Alikhani M
        • Alikhani M
        • Alansari S
        • et al.
        Therapeutic effect of localized vibration on alveolar bone of osteoporotic rats.
        PLoS One. 2019; 14e0211004
        • Ben-Ami Y
        • Lewinson D
        • Silbermann M.
        Structural characterization of the mandibular condyle in human fetuses: light and electron microscopy studies.
        Acta Anat (Basel). 1992; 145: 79-87
        • Hinton RJ
        • Carlson DS.
        Regulation of growth in mandibular condylar cartilage.
        Semin Orthod. 2005; 11: 209-218
        • Copray JC
        • Jansen HW
        • Duterloo HS.
        Growth and growth pressure of mandibular condylar and some primary cartilages of the rat in vitro.
        Am J Orthod Dentofacial Orthop. 1986; 90: 19-28
        • Rabie AB
        • Tang GH
        • Xiong H
        • Hägg U
        PTHrP regulates chondrocyte maturation in condylar cartilage.
        J Dent Res. 2003; 82: 627-631
        • Lane Smith R
        • Trindade MC
        • Ikenoue T
        • et al.
        Effects of shear stress on articular chondrocyte metabolism.
        Biorheology. 2000; 37: 95-107
        • Lee DA
        • Bader DL.
        Compressive strains at physiological frequencies influence the metabolism of chondrocytes seeded in agarose.
        J Orthop Res. 1997; 15: 181-188
        • Shelton JC
        • Bader DL
        • Lee DA.
        Mechanical conditioning influences the metabolic response of cell-seeded constructs.
        Cells Tissues Organs. 2003; 175: 140-150
        • Copray JC
        • Jansen HW
        • Duterloo HS.
        Effects of compressive forces on proliferation and matrix synthesis in mandibular condylar cartilage of the rat in vitro.
        Arch Oral Biol. 1985; 30: 299-304
        • Yang X
        • Vezeridis PS
        • Nicholas B
        • Crisco JJ
        • Moore DC
        • Chen Q.
        Differential expression of type X collagen in a mechanically active 3-D chondrocyte culture system: a quantitative study.
        J Orthop Surg Res. 2006; 1: 15
        • Teixeira CC
        • Abdullah F
        • Alikhani M
        • et al.
        Orthopedic effect of dynamic loading on condylar cartilage.
        Innovation. 2022; 1: e1https://doi.org/10.30771/2022.2
        • Elder SH
        • Goldstein SA
        • Kimura JH
        • Soslowsky LJ
        • Spengler DM.
        Chondrocyte differentiation is modulated by frequency and duration of cyclic compressive loading.
        Ann Biomed Eng. 2001; 29: 476-482
        • Junbo W
        • Sijia L
        • Hongying C
        • Lei L
        • Pu W.
        Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis.
        BMC Musculoskelet Disord. 2017; 18: 260
        • McCann MR
        • Yeung C
        • Pest MA
        • et al.
        Whole-body vibration of mice induces articular cartilage degeneration with minimal changes in subchondral bone.
        Osteoarthritis and Cartilage. 2017; 25: 770-778
        • Tirkkonen L
        • Halonen H
        • Hyttinen J
        • et al.
        The effects of vibration loading on adipose stem cell number, viability and differentiation towards bone-forming cells.
        J R Soc Interface. 2011; 8: 1736-1747
        • Kim IS
        • Song YM
        • Lee B
        • Hwang SJ.
        Human mesenchymal stromal cells are mechanosensitive to vibration stimuli.
        J Dent Res. 2012; 91: 1135-1140
        • Zhang C
        • Li J
        • Zhang L
        • et al.
        Effects of mechanical vibration on proliferation and osteogenic differentiation of human periodontal ligament stem cells.
        Arch Oral Biol. 2012; 57: 1395-1407
        • Prè D
        • Ceccarelli G
        • Visai L
        • et al.
        High-frequency vibration treatment of human bone marrow stromal cells increases differentiation toward bone tissue.
        Bone Marrow Res. 2013; 2013803450
        • Uzer G
        • Pongkitwitoon S
        • Ete Chan M
        • Judex S
        Vibration induced osteogenic commitment of mesenchymal stem cells is enhanced by cytoskeletal remodeling but not fluid shear.
        J Biomech. 2013; 46: 2296-2302
        • Chen X
        • He F
        • Zhong DY
        • Luo ZP.
        Acoustic-frequency vibratory stimulation regulates the balance between osteogenesis and adipogenesis of human bone marrow-derived mesenchymal stem cells.
        BioMed Res Int. 2015; 2015540731
        • Pongkitwitoon S
        • Uzer G
        • Rubin J
        • Judex S.
        Cytoskeletal configuration modulates mechanically induced changes in mesenchymal stem cell osteogenesis, morphology, and stiffness.
        Sci Rep. 2016; 6: 34791
        • Marędziak M
        • Lewandowski D
        • Tomaszewski KA
        • Kubiak K
        • Marycz K.
        The effect of low-magnitude low-frequency vibrations (LMLF) on osteogenic differentiation potential of human adipose derived mesenchymal stem cells.
        Cell Mol Bioeng. 2017; 10: 549-562
        • Lu Y
        • Zhao Q
        • Liu Y
        • et al.
        Vibration loading promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells via p38 MAPK signaling pathway.
        J Biomech. 2018; 71: 67-75
        • Dean D.
        Facial growth.
        Am J Phys Anthropol. 1991; 86 (3rd ed. By D.H. Enlow. Philadelphia: W. B. Saunders. 1990. 576 pp. $79.00 (cloth)): 90-92
        • Paulsen HU.
        Morphological changes of the TMJ condyles of 100 patients treated with the Herbst appliance in the period of puberty to adulthood: a long-term radiographic study.
        Eur J Orthod. 1997; 19: 657-668
        • Nishimura R
        • Hata K
        • Takahata Y
        • Murakami T
        • Nakamura E
        • Yagi H.
        Regulation of cartilage development and diseases by transcription factors.
        J Bone Metab. 2017; 24: 147-153
        • Bielajew BJ
        • Hu JC
        • Athanasiou KA.
        Collagen: quantification, biomechanics, and role of minor subtypes in cartilage.
        Nat Rev Mater. 2020; 5: 730-747
        • Djouad F
        • Bony C
        • Canovas F
        • et al.
        Transcriptomic analysis identifies Foxo3A as a novel transcription factor regulating mesenchymal stem cell chrondrogenic differentiation.
        Cloning Stem Cells. 2009; 11: 407-416
        • Kronenberg HM.
        Developmental regulation of the growth plate.
        Nature. 2003; 423: 332-336
        • Shibukawa Y
        • Young B
        • Wu C
        • et al.
        Temporomandibular joint formation and condyle growth require Indian hedgehog signaling.
        Dev Dyn. 2007; 236: 426-434
        • Carlevaro MF
        • Cermelli S
        • Cancedda R
        • Descalzi Cancedda F
        Vascular endothelial growth factor (VEGF) in cartilage neovascularization and chondrocyte differentiation: auto-paracrine role during endochondral bone formation.
        J Cell Sci. 2000; 113: 59-69
        • Gerber HP
        • Vu TH
        • Ryan AM
        • Kowalski J
        • Werb Z
        • Ferrara N.
        VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation.
        Nat Med. 1999; 5: 623-628
        • Komori T.
        Regulation of osteoblast differentiation by transcription factors.
        J Cell Biochem. 2006; 99: 1233-1239
        • Nakashima K
        • Zhou X
        • Kunkel G
        • et al.
        The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation.
        Cell. 2002; 108: 17-29
        • Teixeira CC
        • Liu Y
        • Thant LM
        • Pang J
        • Palmer G
        • Alikhani M.
        FoxO1, a novel regulator of osteoblast differentiation and skeletogenesis.
        J Biol Chem. 2010; 285: 31055-31065
        • Ota T
        • Chiba M
        • Hayashi H.
        Vibrational stimulation induces osteoblast differentiation and the upregulation of osteogenic gene expression in vitro.
        Cytotechnology. 2016; 68: 2287-2299
        • Stein GS
        • Lian JB.
        Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype.
        Endocr Rev. 1993; 14: 424-442