Like bone mass, bone quality is specified in development, actively maintained postnatally, and disrupted by disease. The roles of osteoblasts, osteoclasts, and osteocytes in the regulation of bone mass are increasingly well defined. However, the cellular and molecular mechanisms by which bone quality is regulated remain unclear. Proteins that remodel bone extracellular matrix, such as the collagen‐degrading matrix metalloproteinase (MMP)‐13, are likely candidates to regulate bone quality. Using MMP‐13–deficient mice, we examined the role of MMP‐13 in the remodeling and maintenance of bone matrix and subsequent fracture resistance. Throughout the diaphysis of MMP‐13–deficient tibiae, we observed elevated nonenzymatic cross‐linking and concentric regions of hypermineralization, collagen disorganization, and canalicular malformation. These defects localize to the same mid‐cortical bone regions where osteocyte lacunae and canaliculi exhibit MMP‐13 and tartrate‐resistant acid phosphatase (TRAP) expression, as well as the osteocyte marker sclerostin. Despite otherwise normal measures of osteoclast and osteoblast function, dynamic histomorphometry revealed that remodeling of osteocyte lacunae is impaired in MMP‐13^−/− bone. Analysis of MMP‐13^−/− mice and their wild‐type littermates in normal and lactating conditions showed that MMP‐13 is not only required for lactation‐induced osteocyte perilacunar remodeling, but also for the maintenance of bone quality. The loss of MMP‐13, and the resulting defects in perilacunar remodeling and matrix organization, compromise MMP‐13^−/− bone fracture toughness and postyield behavior. Taken together, these findings demonstrate that osteocyte perilacunar remodeling of mid‐cortical bone matrix requires MMP‐13 and is essential for the maintenance of bone quality. © 2012 American Society for Bone and Mineral Research.

It was hypothesized that applying the polymer-induced liquid-precursor (PILP) system to artificial lesions would result in time-dependent functional remineralization of carious dentin lesions that restores the mechanical properties of demineralized dentin matrix. 140 µm deep artificial caries lesions were remineralized via the PILP process for 7–28 days at 37°C to determine temporal remineralization characteristics. Poly-L-aspartic acid (27 KDa) was used as the polymeric process-directing agent and was added to the remineralization solution at a calcium-to-phosphate ratio of 2.14 (mol/mol). Nanomechanical properties of hydrated artificial lesions had a low reduced elastic modulus (E_R = 0.2 GPa) region extending about 70 μm into the lesion, with a sloped region to about 140 μm where values reached normal dentin (18–20 GPa). After 7 days specimens recovered mechanical properties in the sloped region by 51% compared to the artificial lesion. Between 7–14 days, recovery of the outer portion of the lesion continued to a level of about 10 GPa with 74% improvement. 28 days of PILP mineralization resulted in 91% improvement of E_R compared to the artificial lesion. These differences were statistically significant as determined from change-point diagrams. Mineral profiles determined by micro x-ray computed tomography were shallower than those determined by nanoindentation, and showed similar changes over time, but full mineral recovery occurred after 14 days in both the outer and sloped portions of the lesion. Scanning electron microscopy and energy dispersive x-ray analysis showed similar morphologies that were distinct from normal dentin with a clear line of demarcation between the outer and sloped portions of the lesion. Transmission electron microscopy and selected area electron diffraction showed that the starting lesions contained some residual mineral in the outer portions, which exhibited poor crystallinity. During remineralization, intrafibrillar mineral increased and crystallinity improved with intrafibrillar mineral exhibiting the orientation found in normal dentin or bone.

Understanding periodontal ligament (PDL) biology and developing an effective treatment for bone and PDL damage due to periodontitis have been longstanding aims in dental medicine. Here, we first demonstrated by cell lineage tracing and mineral double‐labeling approaches that murine PDL progenitor cells display a 2‐ and 3‐fold higher mineral deposition rate than the periosteum and endosteum at the age of 4 weeks, respectively. We next proved that the pathologic changes in osteocytes (Ocys; changes from a spindle shape to round shape with a >50% reduction in the dendrite number/length, and an increase in SOST) are the key pathologic factors responsible for bone and PDL damage in periostin‐null mice (a periodontitis animal model) using a newly developed 3‐dimensional FITC‐Imaris technique. Importantly, we proved that deleting the Sost gene (a potent inhibitor of WNT signaling) or blocking sclerostin function by using the mAb in this periodontitis model significantly restores bone and PDL defects ( n = 4‐5; P < 0.05). Together, identification of the key contribution of the PDL in normal alveolar bone formation, the pathologic changes of the Ocys in periodontitis bone loss, and the novel link between sclerostin and Wnt signaling in the PDL will aid future drug development in the treatment of patients with periodontitis.—Ren, Y., Han, X., Ho, S. P., Harris, S. E., Cao, Z., Economides, A. N., Qin, C., Ke, H., Liu, M., Feng, J. Q. Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model. FASEB J . 29, 2702‐2711 (2015). www.fasebj.org