Researchers from Tokyo Medical and Dental University(TMDU), the Japan Agency for Medical Research and Development, and Kyoto University found that mice that ate foods requiring higher chewing force showed increased bone formation, impacting jawbone shape.
Tokyo, Japan – Throughout an animal’s lifespan, bone tissue in the skeleton is continuously restructured in response to changes in applied force, such as those associated with exercise and locomotion.
Examining how the structure of the jawbone varies with the intense chewing force, or masticatory force, may illuminate the mechanisms that lead to the reconstruction of bone tissue.
Masamu Inoue and Takehito Ono of Tokyo Medical and Dental University (TMDU) have now uncovered how and under what circumstances jawbone reconstruction takes place.
Although previous studies found that the hardness of food is correlated with jaw structure, it was not yet clear whether masticatory force could directly impact bone structure. In this study, the researchers uncovered new information about the cellular and molecular changes that enable bone to adapt to changes in mechanical stress.
They did this by creating a novel mouse model of increased mastication in which mice were fed harder foods (hard diet: HD) to increase chewing force.
They predicted increased chewing directly leads to changes in jawbone structure using a computer simulation.
Histological and gene expression analyses revealed that the mechanical loading onto the jawbone changes cytokine expression of the osteocytes in the bone, resulting in enhanced bone formation.
They recently published their findings in Scientific Reports.
“Although there was existing evidence for the correlation between variations in facial profile and differences in mastication force, evidence for causation was lacking,” says Masamu Inoue, co-first author.
“Additionally, the absence of an animal model of increased mastication made it difficult to study this topic in prior research.”
The researchers found that the width of the masseter muscle, which is critical for mastication, increased in the HD-fed mice.
The HD led to more activation in the primary motor cortex of the brain, which controls the masticatory muscles.
Thus, the HD increased chewing and the amount of force applied to the jawbone.
In vivo micro-computed tomography (micro-CT) analysis showed that mechanical load onto the jawbone by the HD affected its shape, in the way that predicted by the computer simulation.
The simulation also indicated that these morphological changes redistributed the mechanical stress generated in the bone by the HD, indicating that jawbone is able to adapt its shape to changes in mechanical force.
Additionally, they found that increasing the force applied to the jawbone stimulated osteocytes to produce more IGF-1, one of main growth factors that promotes bone formation. This alteration led to bone formation, resulting in morphological changes in the jawbone.
“Our data indicate that masticatory force can prompt changes in facial structure by modulating the function of cells that regulate bone reconstruction,” says co-author Tomoki Nakashima.
“This discovery – that increased chewing itself can directly change the shape of the jawbone – could facilitate the development of treatments for skeletal abnormalities, such as jaw deformities.”
In recent decades, it has become clear that the majority of modern human cranial shape variation is congruent with a null model of neutral evolution, with relatively few morphological regions being subject to diversifying selection (e.g., 10–19).
However, there appear to be two major exceptions to this general pattern.
Aspects of facial morphology, and particularly nasal morphology, are likely to have been subject to diversifying natural selection in response to climatic conditions (11, 20–22), which would explain why facial shape is correlated with climate when cold-adapted populations are included (13, 18).
Second, it has been found (14, 15) that global patterns of mandibular variation do not follow a model of neutral evolution.
If the null model of evolutionary neutrality can be rejected for global patterns of human mandibular variation, alternative nonneutral hypotheses must be considered.
One of the most obvious alternative models is that agricultural populations will experience different biomechanical or selective pressures on mandibular shape than hunter-gatherers, such that modifications have occurred either via phenotypic plasticity or natural selection.
Previous morphometric studies (23, 24) found some geographical patterning in mandibular morphology, as well as a signal of climatic and/or masticatory plasticity.
However, hunter-gatherer and agricultural populations have never explicitly been compared at a global level to evaluate the likely role of subsistence economy in the evolution of the mandible.
Here, this hypothesis is tested by comparing (using Mantel tests) pairwise population distance matrices based on mandibular shape data (Fig. 1) against distance matrices based on neutral genetic, geographical, climatic, and subsistence data (characterized in four ways).
To provide a baseline against which to evaluate these results, the same analyses were also repeated for the cranium and subsets of the cranium (Fig. 2) believed to be related to masticatory function (palatomaxilla, zygotemporal, and temporal lines) and those previously shown to fit a neutral model of variation (cranial vault and chondrocranium). In all cases, the data were collected on the same individuals representing 11 globally distributed populations (Table 1), of which six were categorized as agriculturalist and five as hunter-gatherer (Table 2).
Table 1.
Matched global population data used
| Population | Subsistence economy* | Classical genetics† | Morphology: Museum collected | Cranial (n) | Mandible (n) | Geographical coordinates |
| Ibo | Ibo | Yoruba/Ibo | NHM | 30 | 30 | 7.5, 5.0 |
| Central African | Mbuti | Biaka | NHM, MH | 21 | 19 | 4.0, 17.0 |
| San | Kung San | San | NHM, MH, AMNH, NHMW, DC | 31 | 23 | −21.0, 20.0 |
| Chinese (Han) | Chekiang | Han Chinese | NHMW | 30 | 27 | 32.5, 114.0 |
| Japanese | Japanese | Japanese | MH | 30 | 30 | 38.0, 138.0 |
| Mongolian | Khalka/Chahar | Mongol | MH | 30 | 30 | 45.0, 111.0 |
| Italian | Romans | Italians | NHMW | 30 | 19 | 46.0, 10.0 |
| Hawikuh | Pima | Pima | SNMNH | 30 | 30 | 33.5, −109.0 |
| Alaskan Inuit | Nunamiut | Alaskan Inuit | AMNH | 30 | 30 | 69.0, −158.0 |
| Greenland Inuit | Greenland | Greenland Inuit | SNMNH | 30 | 30 | 70.5, −53.0 |
| Australian | Aranda | Aborigine | DC | 30 | 27 | −22.0, 126.0 |
| Total | 322 | 295 |
- AMNH, American Museum of Natural History (New York); DC, Duckworth Collection (Cambridge, United Kingdom); MH, Musée de l’Homme (Paris); NHM, Natural History Museum (London); NHMW, Das Naturhistorische Museum, Wien (Vienna); SNMNH, Smithsonian National Museum of Natural History (Washington).
- *Data collated from the Corrected Ethnographic Atlas, available online at http://eclectic.ss.uci.edu/ (44).
- †Data collated from Cavalli-Sforza et al. (35).
Table 2.
Quantitative data on subsistence economy collated for each population
| Population | Predominant subsistence economy | Gathering | Hunting | Fishing | Animal husbandry | Agriculture | Milking |
| Ibo | Extensive agriculture | 0–5% | 0–5% | 0–5% | 6–15% | 86–100% | 1 |
| Italians | Intensive agriculture | 0–5% | 0–5% | 16–25% | 16–25% | 56–65% | 2 |
| Japanese | Intensive agriculture | 0–5% | 0–5% | 6–15% | 6–15% | 76–85% | 1 |
| Chinese | Intensive agriculture | 0–5% | 0–5% | 6–15% | 6–15% | 76–85% | 1 |
| Mongolian | Mostly pastoralism | 0–5% | 6–15% | 0–5% | 76–85% | 6–15% | 2 |
| Hawikuh | Intensive agriculture | 26–35% | 6–15% | 6–15% | 0–5% | 46–55% | 1 |
| Biaka/Mbuti | Mostly hunting | 26–35% | 66–75% | 0–5% | 0–5% | 0–5% | 1 |
| San | Mostly gathering | 76–85% | 16–25% | 0–5% | 0–5% | 0–5% | 1 |
| Alaskan | Mostly hunting | 6–15% | 66–75% | 16–25% | 0–5% | 0–5% | 1 |
| Greenland | Mostly fishing | 6–15% | 16–25% | 66–75% | 0–5% | 0–5% | 1 |
| Australian | Mostly gathering | 56–65% | 36–45% | 0–5% | 0–5% | 0–5% | 1 |
- For each category of subsistence dependence, the following ordinal scale was used: 0 = 0–5%, 1 = 6–15%, 2 = 16–25%, 3 = 26–35%, 4 = 36–45%, 5 = 46–55%, 6 = 56–65%, 7 = 66–75%, 8 = 76–85%, 9 = 86–100%. The predominant subsistence economy assigned in the Ethnographic Atlas database was used to assign populations into two groups: agriculturalist/pastoralist and hunter/gatherer/fishers. For the milking variable, 0 = missing, 1 = little/none, 2 = more often than sporadically.
Results
Overall, the results (Table 3) show that the global pattern of mandibular morphology strongly reflects the dichotomous distinction between “hunter-gatherer” and “agricultural/pastoralist” subsistence economy, irrespective of the specific geographical location or population history of each population.
In comparisons of morphology and genetics, only the mandible and the palatomaxilla were not significantly correlated with genetic patterns, supporting the notion (14, 15) that the mandible does not reflect neutral population history.
Given that the palatomaxilla is morphologically integrated with the mandible via dental occlusion, it is not unexpected that it follows a similar nonneutral pattern.
Perhaps surprisingly, the mandible does pattern geographically, although the relationship between mandibular and geographical distance is much weaker (r = 0.44) than for the cranium (r = 0.72).
Nicholson and Harvati (24) also found a geographical patterning in their analysis of modern human mandibular variation, which they interpreted as being related to climatic effects as well as population history.
All morphological regions, except for the temporal lines, were significantly correlated with climate, although these correlations disappeared once neutral genetic distance was controlled for.
This supports previous studies (e.g., 16, 19) suggesting that climatically driven diversifying selection has played a relatively minor role in generating global patterns of cranial variation. However, aspects of facial variation associated with thermoregulation were deliberately not tested here.
Thus, the results do not negate the possibility of climatically driven natural selection on facial morphology in cold-adapted populations (e.g., 11, 18, 20–22).
Table 3.
Results of Mantel and partial Mantel tests performed
| Nonmasticatory | Masticatory | ||||||
| Cranium* | Chondro | Vault | Mandible | Palatomax | Zygotemp | Templines | |
| Mantel tests | |||||||
| Genetics | 0.61 (0.002) | 0.54 (0.001) | 0.62 (0.001) | 0.23 (0.149) | 0.18 (0.179) | 0.50 (0.004) | 0.38 (0.010) |
| Geography | 0.72 (0.001) | 0.79 (0.001) | 0.63 (0.001) | 0.44 (0.010) | 0.19 (0.188) | 0.70 (0.001) | 0.52 (0.002) |
| Climate | 0.49 (0.002) | 0.26 (0.007) | 0.38 (0.016) | 0.38 (0.009) | 0.32 (0.021) | 0.38 (0.015) | 0.20 (0.166) |
| Subsistence 1† | 0.15 (0.166) | 0.23 (0.075) | 0.19 (0.091) | 0.31 (0.032) | 0.32 (0.024) | 0.22 (0.097) | 0.09 (0.453) |
| Subsistence 2† | 0.13 (0.340) | 0.12 (0.388) | 0.20 (0.122) | 0.25 (0.041) | 0.28 (0.036) | 0.11 (0.395) | 0.02 (0.893) |
| Subsistence 3† | 0.26 (0.052) | 0.25 (0.080) | 0.30 (0.022) | 0.37 (0.008) | 0.31 (0.031) | 0.27 (0.058) | 0.12 (0.375) |
| Subsistence 4† | 0.19 (0.100) | 0.22 (0.079) | 0.23 (0.057) | 0.32 (0.012) | 0.30 (0.037) | 0.22 (0.093) | 0.07 (0.565) |
| Partial Mantel tests (genetics controlled for) | |||||||
| Climate | 0.39 (0.018) | 0.10 (0.486) | 0.24 (0.071) | 0.33 (0.033) | 0.28 (0.051) | 0.26 (0.061) | — |
| Subsistence 1† | — | — | — | 0.31 (0.017) | 0.32 (0.034) | — | — |
| Subsistence 2† | — | — | — | 0.26 (0.045) | 0.28 (0.040) | — | — |
| Subsistence 3† | — | — | 0.31 (0.021) | 0.36 (0.014) | 0.30 (0.029) | — | — |
| Subsistence 4† | — | — | — | 0.31 (0.017) | 0.30 (0.040) | — | — |
| Partial Mantel test (genetics, climate, and geography controlled for) | |||||||
| Subsistence 3† | 0.31 (0.045) | 0.34 (0.032) | 0.34 (0.028) | 0.38 (0.009) | 0.28 (0.036) | 0.31 (0.032) | 0.09 (0.477) |
- Correlation coefficients (P values in parentheses) for Mantel and partial Mantel test comparisons of morphological distance matrices and genetic, geographical, climatic, and subsistence distance matrices. Nonsignificant results (P > 0.05 for full, P > 0.017 for 3-way partial, and P > 0.010 for 5-way partial Mantel tests) are shown in bold. Chondro, chondrocranium (basicranium); Palatomax, palate and maxilla region; Templines, insertions of the temporalis muscles; Zygotemp, zygomatic and temporal region (Fig. 2 and Table S2).
- ↵*Cranium refers to the full cranial configuration, including the vault, face, and base.
- ↵†Subsistence 1, binary matrix; Subsistence 2, quantitative data (Table 2); Subsistence 3, hunting and fishing treated as single variable; Subsistence 4, horticulture and animal husbandry treated as single variable.
Irrespective of how differences in subsistence economy were quantified, the mandible and the palatomaxilla were significantly correlated with subsistence, whereas the remaining regions of the cranium were not.
In the case of the third subsistence matrix (where hunting and fishing were treated equally), the vault was also significantly correlated, but this disappeared once population history was controlled for.
Similarly, the relationship between the palatomaxilla and subsistence economy disappeared once population history was controlled for. In contrast, the mandible remained correlated with subsistence economy, even following Bonferroni correction.
The only exception to this was in the case of subsistence matrix 2, where hunting and fishing are treated separately, suggesting that this categorization of subsistence creates artificial differences that do not actually affect the morphology of the mandible.
Moreover, in contrast to all cranial regions tested, a five-way partial Mantel test (α = 0.01) between mandibular variation and the most strongly correlated matrix of subsistence difference (matrix 3) was significant (r = 0.38, P = 0.009), demonstrating that mandibular distance remains significantly correlated with subsistence even when the potentially confounding effects of genetics, geography, and climate are all controlled for (Table 3).
Fig. 3 illustrates the major mandibular shape variation associated with differences in subsistence economy.
The first and second principal components (PCs), which, together, account for almost 33% of the total shape variation, effectively distinguish between agriculturalists (open symbols) and nonagriculturalists (closed symbols).
Despite overlap among individual population samples, agriculturalist populations have relatively shorter and broader mandibles with taller and more angled rami and coronoid processes, whereas hunter-gatherer populations have longer and narrower mandibles with short and upright rami and coronoid processes.
More information: Masamu Inoue et al, Forceful mastication activates osteocytes and builds a stout jawbone, Scientific Reports (2019). DOI: 10.1038/s41598-019-40463-3
Journal information: Scientific Reports
Provided by Tokyo Medical and Dental University
