Highlights d Cranial sutures represent an NGF-expressing domain in which sensory nerves transit d Monocyte/macrophage-derived Ngf induces skeletal innervation and bone repair d Blocking NGF-TrkA signaling delays skeletal re-innervation and blunts bone repair
Pulled elbow is a common upper extremity injury in children. We present a retrospective study of 2331 pulled elbow cases examined in our hospital over the last ten years. All pediatric patients with a diagnosis of pulled elbow from January 2002 to December 2011 were retrospectively reviewed according to sex, age, affected arm, recurrence rate, mechanism of injury and treatment outcomes. There is no significant sex difference. The frequency of injury peaked for both boys and girls at 6 months and 2 years of age. The left arm was more affected than the right. The recurrence rate was 14%. In about 50% of cases, the cause of injury was forcible traction to the forearm. Almost all of the splinted patients, caused by severe pain or lack of mobility of the affected limb following reduction, recovered within 2 weeks, but 2 were later diagnosed with a fracture. For infants less than 1 year old, injury can often occur when rolling over. For children 1 year old or older the left arm is more commonly affected, and the frequency of injuries to the left arm increases with age, possibly because the left hand is commonly held by the guardian’s dominant right hand and faster development of muscle strength in the child’s dominant right arm works toward preventing injury to that arm with age.
Implantation into osteoporotic bone constitutes a challenging problem because of early migration or loosening of the implant, which is primarily due to insufficient initial fixation in porotic bone. Therefore, it is desirable to provide implants with a capacity for early bone bonding. We have achieved conferring early bone bonding ability to titanium metal by releasing strontium ions or magnesium ions. Our treatment is promising for clinical applications to achieve early bone bonding of orthopedic or dental Ti-based implants.
Bone regeneration following injury is initiated by inflammatory signals and occurs in association with infiltration by sensory nerve fibers. Together, these events are believed to coordinate angiogenesis and tissue reprogramming, but the mechanism of coupling immune signals to reinnervation and osteogenesis is unknown. Here, we found that nerve growth factor (NGF) is expressed following cranial bone injury and signals via p75 in resident mesenchymal osteogenic precursors to affect their migration into the damaged tissue. Mice lacking
Ngf
in myeloid cells demonstrated reduced migration of osteogenic precursors to the injury site with consequently delayed bone healing. These features were phenocopied by mice lacking
p75
in
Pdgfra
+
osteoblast precursors. Single-cell transcriptomics identified mesenchymal subpopulations with potential roles in cell migration and immune response, altered in the context of
p75
deletion. Together, these results identify the role of p75 signaling pathway in coordinating skeletal cell migration during early bone repair.
Bone repair requires the tightly
regulated control of multiple
intrinsic and extrinsic cell types and signaling pathways. One of
the positive regulatory signaling pathways in membranous and endochondral
bone healing is the Hedgehog (Hh) signaling family. Here, a novel
therapeutic liposomal delivery vector was developed by self-assembly
of an Hh-activating cholesterol analog with an emulsifier, along with
the addition of Smoothened agonist (SAG) as a drug cargo, for the
enhancement of Hh signaling in bone regeneration. The drug-loaded
nanoparticulate agonists of Hh signaling were immobilized onto trabecular
bone-mimetic apatite-coated 3D scaffolds using bioinspired polydopamine
adhesives to ensure favorable microenvironments for cell growth and
local therapeutic delivery. Results showed that SAG-loaded liposomes
induced a significant and dose-dependent increase in Hh-mediated osteogenic
differentiation, as evidenced by in vitro analysis
of bone marrow stromal cells, and in vivo calvarial
bone healing, as evidenced using all radiographic parameters and histomorphometric
analyses. Moreover, favorable outcomes were achieved in comparison
to standards of care, including collagen sponge-delivered rBMP2 or
allograft bone. In summary, this study demonstrates using a nanoparticle
packaged Hh small molecule as a widely applicable bone graft substitute
for robust bone repair.
Tissue resident mesenchymal stem/stromal cells (MSCs) occupy perivascular spaces. Profiling human adipose perivascular mesenchyme with antibody arrays identified 16 novel surface antigens, including endolysosomal protein CD107a. Surface CD107a expression segregates MSCs into functionally distinct subsets. In culture, CD107alow cells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107ahigh cells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107alow cells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107ahigh cells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107alow cells are precursors of CD107ahigh cells. These results document the molecular and functional diversity of perivascular regenerative cells, and show that relocation to cell surface of a lysosomal protein marks the transition from osteo- to adipogenic potential in native human MSCs, a population of substantial therapeutic interest.
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