The biology of bone healing is a rapidly developing science. Advances in transgenic and gene-targeted mice have enabled tissue and cell-specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing— coupled with the heterogeneity of animal models—renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment.

Background:Literature on arthroscopic stabilization in adolescent patients participating in collision and contact sports is limited, as most studies include adolescents within a larger sample group comprised primarily of adults.Purpose:To review the outcomes of arthroscopic Bankart repair for anterior shoulder instability in an adolescent population participating in collision and contact sports.Study Design:Case series; Level of evidence, 4.Methods:This retrospective review included 39 shoulders in 37 adolescent (≤19 years) athletes who underwent primary arthroscopic Bankart repair using suture anchors with at least 2-year follow-up. All patients had a history of trauma to their shoulder resulting in an anterior dislocation. Outcome measures included patient satisfaction, the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score. Recurrence of dislocation and return to sporting activity were also assessed.Results:The mean age at the time of surgery was 16.9 years (range, 15-19 years), and the mean follow-up was 6.3 years (range, 4.3-10.0 years); 58.6% of patients participated in collision sports. Time to surgery after the initial dislocation episode was 9.2 months (range, 0.5-36.2 months). Four shoulders (10.3%) had dislocation events postoperatively. The majority (78.1%) of patients returned to sports at the same level of competition. Mean VAS was 0.49 ± 1.0, and the mean ASES and Rowe scores were 92.8 ± 12.6 and 85.0 ± 24.2, respectively. Univariate analyses demonstrated that subjective functional outcomes were negatively correlated with recurrence (ASES, P = .005; Rowe, P = .001) and failure to return to sport (ASES, P = .016; Rowe, P = .004). Independent variables shown to have no significant relationship to functional outcomes included age, follow-up, number of preoperative dislocations, time to surgery, sport classification, competition level, tear extent, number of anchors, concurrent Hill-Sachs lesion, and repair of a superior labral anterior-posterior (SLAP) lesion.Conclusion:Arthroscopic Bankart repair is an effective surgical option for traumatic shoulder instability in adolescents participating in collision and contact sports. At a minimum 4-year follow-up, arthroscopic Bankart repair effectively restored stability in 90% of cases; 80% returned to their preinjury level of sport.

The R-spondin family of proteins are Wnt agonists, and the complete embryonic disruption of Rspo2 results in skeletal developmental defects that recapitulate the phenotype observed with Lrp5/6 deficiency. Previous work has shown that R-spondin-2 (Rspo2, RSPO2) is both highly expressed in Wnt-stimulated pre-osteoblasts and its overexpression induces osteoblast differentiation in the same cells, supporting its putative role as a positive autocrine regulator of osteoblastogenesis. However, the role of Rspo2 in regulating osteoblastogenesis and bone formation in postnatal bone has not been explored. Here we show that limb-bud progenitor cells from Rspo2 knockout mice undergo reduced mineralization during osteoblastogenesis in vitro and have a corresponding alteration in their osteogenic gene expression profile. We also generated the first Rspo2 conditional knockout (Rspo2floxed) mouse and disrupted Rspo2 expression in osteoblast-lineage cells by crossing to the Osteocalcin-Cre mouse line (Ocn-Cre + Rspo2f/f). Ocn-Cre + Rspo2f/f male and female mice at 1, 3, and 6 months were examined. Ocn-Cre + Rspo2f/f mice are decreased in overall body size compared to their control littermates and have decreased bone mass. Histomorphometric analysis of 1-month-old mice revealed a similar number of osteoblasts and mineralizing surface per bone surface with a simultaneous decrease in mineral apposition and bone formation rates. Consistent with this observation, serum osteocalcin in 3-month-old Ocn-Cre + Rspo2f/f was reduced, and bone marrow-mesenchymal stem cells from Ocn-Cre + Rspo2f/f mice undergo less mineralization in vitro. Finally, gene expression analysis and immunohistochemistry of mature bone shows reduced beta-catenin signaling in Ocn-Cre + Rspo2f/f. Overall, RSPO2 reduces osteoblastogenesis and mineralization, leading to reduced bone mass.

Each year, 33% of US citizens suffer from a musculoskeletal condition that requires medical intervention, with direct medical costs approaching $1 trillion USD per year. Despite the ubiquity of skeletal dysfunction, there are currently limited safe and efficacious bone growth factors in clinical use. Notch is a cell–cell communication pathway that regulates self-renewal and differentiation within the mesenchymal/osteoblast lineage. The principal Notch ligand in bone, Jagged-1, is a potent osteoinductive protein that positively regulates post-traumatic bone healing in animals. This report describes the temporal regulation of Notch during intramembranous bone formation using marrow ablation as a model system and demonstrates decreased bone formation following disruption of Jagged-1 in mesenchymal progenitor cells. Notch gain-of-function using recombinant Jagged-1 protein on collagen scaffolds promotes healing of craniofacial (calvarial) and appendicular (femoral) surgical defects in both mice and rats. Localized delivery of Jagged-1 promotes bone apposition and defect healing, while avoiding the diffuse bone hypertrophy characteristic of the clinically problematic bone morphogenetic proteins. It is concluded that Jagged-1 is a bone-anabolic agent with therapeutic potential for regenerating traumatic or congenital bone defects.