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Tooth extraction triggers alveolar ridge resorption, and when this resorption is extensive, it can complicate subsequent reconstructive procedures that use dental implants. Clinical data demonstrate that the most significant dimensional changes in the ridge occur soon after tooth extraction. Here, we sought to understand whether a correlation existed between the rate at which an extraction socket heals and the extent of alveolar ridge resorption. Maxillary molars were extracted from young and osteoporotic rodents, and quantitative micro–computed tomographic imaging, histology, and immunohistochemistry were used to simultaneously follow socket repair and alveolar ridge resorption. Extraction sockets rapidly filled with new bone via the proliferation and differentiation of Wnt-responsive osteoprogenitor cells and their progeny. At the same time that new bone was being deposited in the socket, tartrate-resistant acid phosphatase–expressing osteoclasts were resorbing the ridge. Significantly faster socket repair in young animals was associated with significantly more Wnt-responsive osteoprogenitor cells and their progeny as compared with osteoporotic animals. Delivery of WNT3A to the extraction sockets of osteoporotic animals restored the number of Wnt-responsive cells and their progeny back to levels seen in young healthy animals and accelerated socket repair in osteoporotic animals back to rates seen in the young. In cases where the extraction socket was treated with WNT3A, alveolar ridge resorption was significantly reduced. These data demonstrate a causal link between enhancing socket repair via WNT3A and preserving alveolar ridge dimensions following tooth extraction. [ABSTRACT FROM AUTHOR]

Summary: Our goal was to evaluate alveolar bone healing in OVX mice, and to assess the functional utility of a WNT-based treatment to accelerate healing in mice with an osteoporotic-like bony phenotype. Introduction: Is osteoporosis a risk factor for dental procedures? This relatively simple question is exceedingly difficult to answer in a clinical setting, for two reasons. First, as an age-related disease, osteoporosis is frequently accompanied by age-related co-morbidities that can contribute to slower tissue repair. Second, the intervals at which alveolar bone repair are assessed in a clinical study are often measured in months to years. This study aimed to evaluate alveolar bone repair in ovariectomized (OVX) mice and provide preclinical evidence to support a WNT-based treatment to accelerate alveolar bone formation. Methods: OVX was performed in young mice to produce an osteoporotic-like bone phenotype. Thereafter, the rate of extraction socket healing and osteotomy repair was assessed. A liposomal WNT3A treatment was tested for its ability to promote alveolar bone formation in this OVX-induced model of bone loss. Results: Bone loss was observed throughout the murine skeleton, including the maxilla, and mirrored the pattern of bone loss observed in aged mice. Injuries to the alveolar bone, including tooth extraction and osteotomy site preparation, both healed significantly slower than the same injuries produced in young controls. Given sufficient time, however, all injuries eventually healed. In OVX mice, osteotomies healed significantly faster if they were treated with L-WNT3A. Conclusions: Alveolar bone injuries heal slower in OVX mice that exhibit an osteoporotic-like phenotype. The rate of alveolar bone repair in OVX mice can be significantly promoted with local delivery of L-WNT3A. [ABSTRACT FROM AUTHOR]

Osteoporosis is associated with decreased bone density and increased bone fragility, but how this disease affects alveolar bone healing is not clear. The objective of this study was to determine the extent to which osteoporosis affects the jaw skeleton and then to evaluate possible mechanisms whereby an osteoporotic phenotype might affect the rate of alveolar bone healing following tooth extraction. Using an ovariectomized mouse model coupled with micro-computed tomographic imaging, histologic, molecular, and cellular assays, we first demonstrated that the appendicular and jaw skeletons both develop osteoporotic phenotypes. Next, we demonstrated that osteoporotic mice exhibit atrophy of the periodontal ligament (PDL) and that this atrophy was accompanied by a reduction in the pool of osteoprogenitor cells in the PDL. The paucity of PDL-derived osteoprogenitor cells in osteoporotic mice was associated with significantly slower extraction socket healing. Collectively, these analyses demonstrate that the jaw skeleton is susceptible to the untoward effects of osteoporosis that manifest as thinner, more porous alveolar bone, PDL thinning, and slower bone repair. These findings have potential clinical significance for older osteopenic patients undergoing reconstructive procedures. [ABSTRACT FROM AUTHOR]

A soft food diet leads to changes in the periodontal ligament (PDL). These changes, which have been recognized for more than a century, are ascribed to alterations in mechanical loading. While these adaptive responses have been well characterized, the molecular, cellular, and mechanical mechanisms underlying the changes have not. Here, we implicate Wnt signaling in the pathoetiology of PDL responses to underloading. We show that Wnt-responsive cells and their progeny in the PDL space exhibit a burst in proliferation in response to mastication. If an animal is fed a soft diet from the time of weaning, then this burst in Wnt-responsive cell proliferation is quelled; as a consequence, both the PDL and the surrounding alveolar bone undergo atrophy. Returning these animals to a hard food diet restores the Wnt signaling in PDL. These data provide, for the first time, a molecular mechanism underlying the adaptive response of the PDL to loading. [ABSTRACT FROM AUTHOR]

Our long-term objective is to devise methods to improve osteotomy site preparation and, in doing so, facilitate implant osseointegration. As a first step in this process, we developed a standardized oral osteotomy model in ovariectomized rats. There were 2 unique features to this model: first, the rats exhibited an osteopenic phenotype, reminiscent of the bone health that has been reported for the average dental implant patient population. Second, osteotomies were produced in healed tooth extraction sites and therefore represented the placement of most implants in patients. Commercially available drills were then used to produce osteotomies in a patient cohort and in the rat model. Molecular, cellular, and histologic analyses demonstrated a close alignment between the responses of human and rodent alveolar bone to osteotomy site preparation. Most notably in both patients and rats, all drilling tools created a zone of dead and dying osteocytes around the osteotomy. In rat tissues, which could be collected at multiple time points after osteotomy, the fate of the dead alveolar bone was followed. Over the course of a week, osteoclast activity was responsible for resorbing the necrotic bone, which in turn stimulated the deposition of a new bone matrix by osteoblasts. Collectively, these analyses support the use of an ovariectomy surgery rat model to gain insights into the response of human bone to osteotomy site preparation. The data also suggest that reducing the zone of osteocyte death will improve osteotomy site viability, leading to faster new bone formation around implants. [ABSTRACT FROM AUTHOR]

We have previously shown that an outer membrane protein, SspA, is prominently induced by salt stress in a photosynthetic bacterium, Rhodobacter sphaeroides f. sp. denitrificans IL106 ( R. sphaeroides). In this study, we investigated the physiological role of SspA under various stress conditions. Using recombinant SspA expressed in Escherichia coli as an antigen, the polyclonal antiserum of SspA was prepared. Western blot analysis demonstrated that SspA was highly induced by salt stress under both anaerobic and aerobic conditions. SspA was also induced, but to a lesser extent, by osmotic and acid stress. It is reduced under heat and cold compared to non-stressed conditions. While sspA-disrupted R. sphaeroides grew normally under anaerobic conditions in either the presence or absence of stress, it displayed significantly retarded growth under aerobic conditions in the dark, especially when osmotic or salt stress were imposed. In addition, the sspA disruptant, but not the wild type, formed cell aggregates when grown under both anaerobic and aerobic conditions, and this phenotype was significantly enhanced under salt-stressed aerobic conditions. Together, our findings suggest that SspA is critical under salt-stressed, aerobic growth conditions. [ABSTRACT FROM AUTHOR]