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 Table of Contents  
ORIGINAL HYPOTHESIS
Year : 2015  |  Volume : 6  |  Issue : 1  |  Page : 6-9

Possible mechanisms of lack of dentin bridge formation in response to calcium hydroxide in primary teeth


1 Department of Pedodontics and Preventive Dentistry, Drs. Sudha and Nageswara Rao Siddhartha Institute of Dental Sciences, Krishna District, Andhra Pradesh, India
2 Department of Oral and Maxillofacial Pathology, Anil Neerukonda Institute of Dental Sciences, Vishakapatnam, Andhra Pradesh, India

Date of Web Publication5-Feb-2015

Correspondence Address:
G R Ravi
Department of Pedodontics and Preventive Dentistry, Drs. Sudha and Nageswara Rao Siddhartha Institute of Dental Sciences Chinnaoutpalli, Gannavaram, Krishna - 521 286, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2155-8213.150863

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  Abstract 

Introduction: The usage of Calcium hydroxide (CaOH2) has wide applications due to the property of osteo-inductive, protective, and antibacterial actions. However, it is not used in primary teeth, as it fails to form reparative dentin and the exact mechanism has not been explained. The hypothesis: The authors propose an explanation that lack of dentin bridge formation in response to (CaOH2) in primary teeth could be multifactorial: inability of the deciduous stem cells to generate complete dentin-pulp-like tissue; the absence of calcium-magnesium-dependent adenosine triphosphatase (Ca-Mg ATPase) in the odontoblasts; the pre-existing predilection of deciduous dentine pulp to form odontoclasts; the solubility of (CaOH2). Evaluation of the hypothesis: The hypothesis discusses the innate traits of the deciduous stem cells that lack the ability to form the dentin bridge, the absence of Ca-Mg ATPase enzyme and increased solubility of (CaOH2) together fail to stimulate the odontoblasts. Alternatively, pre-existing progenitor cells with proclivity to change into odontoclasts may cause internal resorption and hamper formation of reparative dentin.

Keywords: Calcium hydroxide, Ca-Mg ATPase, dentin bridge, deciduous teeth, primary teeth, tooth resorption


How to cite this article:
Ravi G R, Subramanyam R V. Possible mechanisms of lack of dentin bridge formation in response to calcium hydroxide in primary teeth. Dent Hypotheses 2015;6:6-9

How to cite this URL:
Ravi G R, Subramanyam R V. Possible mechanisms of lack of dentin bridge formation in response to calcium hydroxide in primary teeth. Dent Hypotheses [serial online] 2015 [cited 2019 Sep 22];6:6-9. Available from: http://www.dentalhypotheses.com/text.asp?2015/6/1/6/150863


  Introduction Top


Since the introduction of calcium hydroxide (CaOH2) to dentistry by Hermann (1920, 1930), this medicament has been indicated to promote healing in many clinical situations. [1],[2],[3] However, the initial reference to its use has been attributed to Nygren (1838) for the treatment of the "fistula dentalis," while Codman (1851) was the first to attempt to preserve the involved dental pulp. [1] CaOH2 is classically used as the gold standard in biocompatibility tests due to its direct or indirect effect on exposed pulp repair. Some of its indications include direct and indirect pulp capping, apexogenesis, apexification, treatment of root resorption, iatrogenic root perforations, root fractures, replanted teeth, and inter-appointment intra-canal dressing. [4]

The property of stimulating sclerotic and reparative dentin formation and protecting the pulp against thermal stimuli and antibacterial action has prompted for the usage of CaOH2 with increased frequency as a multipurpose agent. [2],[5],[6] However, its usage in primary teeth is selective as it is known to cause chronic inflammation and resorption. Recently a hypothesis was proposed explaining the possible mechanisms for internal resorption of deciduous teeth in presence of CaOH2. The hypothesis revolved around odontoclastogenesis and pre-existing predilection of stem cells to form odontoclasts when using CaOH2. [7]

However, the exact mechanism that prevents CaOH2 to induce hard tissue formation in primary teeth is still not known. At this juncture, two questions need to be answered:

  1. Does CaOH2 fail to stimulate hard tissue formation? or
  2. Does the pulp of deciduous tooth lack inherent capacity to result in reparative dentin formation though stimulated by CaOH2?


These intriguing questions led us to present hypotheses to explain the lack of dentin bridge formation in deciduous teeth.


  The Hypothesis Top


We hypothesize that the lack of dentin bridge formation in deciduous teeth is multi-factorial. Firstly, stem cells of the deciduous teeth are highly proliferative, clonogenic, and have multi-differentiation potential, but lack the ability to generate complete dentin-pulp-like tissue. Secondly, the absence of calcium-magnesium-dependent adenosine triphosphatase (Ca-Mg ATPase) in the odontoblasts in the pulp leads to failure of stimulation of hard tissue formation. Thirdly, the pre-existing predilection of deciduous dentine pulp to form odontoclasts is triggered which in turn overshadows the osteo-inductive activity of CaOH2 and results in resorption. Fourthly, an effective stimulation of the odontoblasts to lay down adequate amount of dentin is compromised due to the solubility of CaOH2. [Figure 1] succinctly depicts all these four hypotheses.
Figure 1: Proposed mechanisms for lack of dentine bridge formation in deciduous tooth pulp in presence of calcium hydroxide (CaOH2)

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  Evaluation of the Hypothesis Top


The primary function of pulp is dentin formation, which begins the moment the peripheral mesenchymal cells differentiate into odontoblasts and start the deposition of collagen matrix, in a sequence of apposition/mineralization that ends with the complete tooth formation. Even after the initial formation, pulp continues to physiologically produce dentin throughout the life of the tooth. Reparative dentin may also be produced in response to physical and/or chemical injuries. Furthermore, the pulp is responsible for the response to different stimuli, which forms its defensive action and includes blood vessel dilatation and permeability, and the presence of inflammatory cells. When the stimulus does not exceed the pulp healing capacity, modification in the dentin-pulp complex may occur, including repair. [8]

CaOH2 is known to produce dentine bridge formation when placed in permanent teeth through various possible mechanisms as shown in [Figure 2]. So why does deciduous tooth pulp fail to form dentin bridge in the presence of CaOH2?
Figure 2: Mechanisms by which calcium hydroxide (CaOH2) may form dentine bridge/reparative dentine in permanent teeth

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Inability of deciduous stem cells to differentiate

The molecular control of odontoblastic differentiation and reparative dentinogenesis is attributed to differential gene expressions, protein activities, and release of signaling molecules from injured pulpal cells. [9] When the injury is removed before pulp damage, a repair process begins [10] and collagen synthesis is accelerated in this phase. [11] The deposition of collagen in the pulp tissue is increased by the action of cytokines. Collagen synthesis may be improved by transforming growth factor (TGF)-β 1 and TGF-β 2 and interleukin (IL)-1α. [12],[13] Fibroblasts, in an inflammatory microenvironment, deposit more amount of collagen during the inflammatory process as opposed to normal conditions. [12] The collagen synthesis by fibroblasts during the inflammatory process is a key event for human pulp repair. [13]

Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic, and have multi-differentiation potential when compared to bone marrow stem cells (BMSCs) and human dental pulp stem cells (hDPSCs) of permanent teeth. [9] When stimulated, they have the ability to differentiate into adipocytes, neural cells, and odontoblasts but not into osteoblasts. However, they exhibit an osteoinductive potential in which the host cells are stimulated to differentiate into bone forming cells. [14] Miura et al. also demonstrated the inability of SHED to generate complete dentin-pulp-like tissue as did hDPSCs, indicating that perhaps they are immature cells. [14] This innate feature of the deciduous pulp stem cells may result in inadequate differentiation of fibroblasts and osteoblasts and therefore do not result in proper hard tissue formation when stimulated by CaOH2.

Ca-ATPase-Mediated hard tissue formation

Enzymatic activities of Ca-Mg ATPase and non-specific alkaline phosphatase (ALPase) are known to be associated with hard tissue formation. [15],[16],[17] However, Ca-Mg ATPase is localized in the Golgi cisternae, cytoplasmic vesicles, and along the outer surface of the pre-secretory and secretory ameloblasts, whereas it is totally absent from the odontoblasts. Inversely, ALPase is localized along the outer surface of the odontoblasts, but almost completely absent from the ameloblasts. [16] Thus, CaOH2-mediated hard tissue formation may not occur in deciduous teeth due to the absence of Ca-Mg ATPase.

Pre-Existing predilection to form odontoclasts

A pre-existing predilection of progenitor cells in deciduous tooth pulp to form odontoclasts probably under the influence of various factors like tartrate-resistant acid phosphatase (TRAP), Receptor Activator of Nuclear FactorκB / ligand (RANK/ RANKL), Macrophage Colony-Stimulating Factor (M-CSF), cytokines, such as TNF-α and interleukins (IL-1α, IL-β, IL-6, IL-11, IL-17), the progenitor cells could be transformed into pre-odontoclasts which in turn transform into odontoclasts. Further, the placement of CaOH2 induces chronic inflammatory response which could influence the macrophages to fuse and form odontoclasts, either through direct stimulation or indirectly by stimulating stromal odontoblasts/fibroblasts. In addition, the loss of predentin could expose mineralized dentin to odontoclasts, making it more vulnerable to resorption. Altogether, the pre-existing propensity for transformation of odontoclasts could be influenced or hastened by placement of CaOH2. [7]

Solubility of calcium hydroxide

CaOH2, in dry powder, suspension, or cement form, has been recommended for the treatment of exposed pulp due to its beneficial properties such as induction of mineralization and inhibition of bacterial growth. [18] Many studies indicate pulp repair and hard tissue barrier formation when exposed pulp tissue is directly capped with different CaOH2 formulations. It has been reported that the high alkaline pH of CaOH2 solutions can solubilize and release some proteins and growth factors from dentin. These events may be responsible for the pulp repair and hard tissue barrier formation. [19]

In spite of these advantages, CaOH2 is soluble in water and acid and its physical properties are deficient. [6],[20] Several cases are mentioned in the literature in which base/liner materials, after some time, are not capable of remaining stable under restorations, leaving the cavity unprotected and the restoration unsupported, which may be due to material dissolution or water sorption. This may occur when the material gets in contact with either dentinal fluid (common in freshly prepared cavities) or aqueous medium (due to marginal infiltration or hydrolytic decomposition). [21],[22],[23],[24]

Although hard-setting CaOH2 cements may induce the formation of dentin bridges, they are not likely to provide an effective long-term seal when facing a bacterial challenge. Within a few years of placement, majority of mechanically exposed and capped pulps show infection and necrosis caused by microleakage of such capping materials and tunnel defects in the dentin bridges. [24],[25] Strength of these cements is relatively low and solubility is relatively high in many instances. [26]

CaOH2 when used in deciduous teeth is known to trigger chronic inflammation. As a consequence, this leads to rapid diffusion of CaOH2 into the edematous fluid depleting the concentration required for proper hard tissue formation. Inadequate levels of CaOH2 may further fail to stimulate the progenitor cells to differentiate into odontoblasts and fibroblasts so as to carry out the hard tissue formation.

Research implications

Lack of CaOH2-induced reparative dentin formation is multifactorial. Though it has been established that there is a lack of reparative dentine formation in response to CaOH2, the exact mechanism is still elusive. Our hypotheses provide explanation as to how this could occur. However, these proposed mechanisms need to be substantiated with scientific evidence. In addition, the high solubility of CaOH2CaOH2CaOH2 and the absence of Ca-Mg ATPase which collectively result in lack of stimulation of progenitor cells to form odontoblasts also need to be investigated.

 
  References Top

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  [Figure 1], [Figure 2]



 

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