Long non-coding RNA MIAT serves as a biomarker of fragility fracture and promotes fracture healing.

BACKGROUND: Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated. METHODS: 90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis. RESULTS: Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation. CONCLUSIONS: LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.

LncRNA MAGI2-AS3 promotes fracture healing through downregulation of miR-223-3p.

BACKGROUND: Long non-coding RNAs (LncRNAs) are recognized as a pivotal element in the processes of fracture healing and the osteogenic differentiation of stem cells. This study investigated the molecular mechanism and regulatory significance of lncRNA MAGI2-AS3 (MAGI2-AS3) in fracture healing. METHODS: Serum levels of MAGI2-AS3 in patients with normal and delayed fracture healing were verified by RT-qPCR assays. The predictive efficacy of MAGI2-AS3 for delayed fracture healing was analyzed by ROC curve. Osteogenic markers were quantified by RT-qPCR assays. MC3T3-E1 cell viability was detected using CCK-8 assay, and flow cytometry was utilized to measure cell apoptosis. The dual-luciferase reporter gene assay was used to determine the targeted binding between MAGI2-AS3 and miR-223-3p. RESULTS: Serum MAGI2-AS3 expression was decreased in patients with delayed fracture healing compared with patients with normal healing. Elevated MAGI2-AS3 resulted in an upregulation of the proliferative capacity of MC3T3-E1 cells and a decrease in mortality, along with increased levels of both osteogenic markers. However, after transfection silencing MAGI2-AS3, the trend was reversed. Additionally, miR-223-3p was the downstream target of MAGI2-AS3 and was controlled by MAGI2-AS3. miR-223-3p mimic reversed the promoting effects of MAGI2-AS3 overexpression on osteogenic marker levels and cell growth, and induced cell apoptosis. CONCLUSION: The upregulation of MAGI2-AS3 may expedite the healing of fracture patients by targeting miR-223-3p, offering a novel biomarker for diagnosing patients with delayed healing.

Modified and alternative bone cements can improve the induced membrane: Critical size bone defect model in rat femur.

BACKGROUND: As a two-stage surgical procedure, Masquelet's technique has been used to care for critical-size bone defects (CSD). We aimed to determine the effects of modified and altered bone cement with biological or chemical enriching agents on the progression of Masquelet's induced membrane (IM) applied to a rat femur CSD model, and to compare the histopathological, biochemical, and immunohistochemical findings of these cements to enhance IM capacity. METHODS: Thirty-five male rats were included in five groups: plain polymethyl methacrylate (PMMA), estrogen-impregnated PMMA (E+PMMA), bone chip added PMMA (BC+PMMA), hydroxyapatite-coated PMMA (HA) and calcium phosphate cement (CPC). The levels of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) were analyzed in intracardiac blood samples collected at the end of 4 weeks of the right femur CSD intervention. All IMs collected were fixed and prepared for histopathological scoring. The tissue levels of rat-specific Transforming Growth Factor-Beta (TGF-ß), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) were analyzed immunohistochemically. RESULTS: Serum levels of BALP and OC were significantly higher in E+PMMA and BC+PMMA groups than those of other groups (P = 0.0061 and 0.0019, respectively). In contrast, TNF-α levels of all groups with alternative bone cement significantly decreased compared to bare PMMA (P = 0.0116). Histopathological scores of E+PMMA, BC+PMMA, and CPC groups were 6.86 ± 1.57, 4.71 ± 0.76, and 6.57 ± 1.51, respectively, which were considerably higher than those of PMMA and HA groups (3.14 ± 0.70 and 1.86 ± 0.69, respectively) (P < 0.0001). Significant increases in TGF-ß and VEGF expressions were observed in E+PMMA and CPC groups (P = 0.0001 and <0.0001, respectively) whereas Runx2 expression significantly increased only in the HA group compared to other groups (P < 0.0001). CONCLUSIONS: The modified PMMA with E and BC, and CPC as an alternative spacer resulted in a well-differentiated IM and increased IM progression by elevating BALP and OC levels in serum and by mediating expressions of TGF-ß and VEGF at the tissue level. Estrogen-supplemented cement spacer has yielded promising findings between modified and alternative bone cement.

Cellular therapies for bone repair: current insights.

Mesenchymal stem cells are core to bone homeostasis and repair. They both provide the progenitor cells from which bone cells are formed and regulate the local cytokine environment to create a pro-osteogenic environment. Dysregulation of these cells is often seen in orthopaedic pathology and can be manipulated by the physician treating the patient. This narrative review aims to describe the common applications of cell therapies to bone healing whilst also suggesting the future direction of these techniques.

Metatarsal Fractures.

Metatarsal fractures are some of the most common fractures reported in the human body. Recent advances in surgical techniques and fixation have helped facilitate healing and improved outcomes for our patients. The treatment goals of metatarsal fractures are to maintain the metatarsal parabola, sagittal position of the metatarsal heads, and a congruent metatarsophalangeal joint. Most of these injuries can be treated nonoperatively, but displaced fractures require surgical intervention to preserve normal gait biomechanics.

Management of non-union of rib fractures secondary to trauma: A scoping review.

OBJECTIVE: Rib fracture non-union is an uncommon complication of traumatic rib fractures. Our objective was to perform a scoping review of the literature for the management of rib fracture non-union. This included analysis of the variations in surgical technique, complications experienced, and reported outcomes. METHODS: We conducted a scoping review and searched databases (MEDLINE, CINAHL, and Embase). We performed abstract and full-text screening, and abstracted data related to pre-operative assessment, surgical technique, complications, and reported outcome measures. RESULTS: We included 29 articles of which 19 were case reports and 10 were case series. The data quality was generally heterogeneous. The studies included 229 patients and the commonest symptoms of rib fracture non-union included chest pain, clicking, dyspnea and deformities. The patients underwent surgical management of rib fracture non-union (excluding first rib fractures) using various techniques. The majority used surgical stabilization of rib fracture with or without a graft. The reported outcomes were inconsistent between studies, but showed high rates of union (>94 %), reduction in reported VAS scores, and improved return to work when included. Implant failure occurred in 10 % of the 229 total patients reported in our studies, the re-operation rate was 13 %, and the overall complication rate was 27 %. CONCLUSION: Surgical management of rib fracture non-union often involving locking plates and screws with or without a graft has been shown in several case reports and series as an effective treatment with acceptable implant failure and complication rates. Surgical management is therefore a viable option for symptomatic patients. Further research is required to determine optimal management strategies that further reduce surgical complications for these patients.

Favourable outcome in survivors of CPR-related chest wall injuries.

BACKGROUND: There is a lack of studies focusing on long-term chest function after chest wall injury due to cardiopulmonary resuscitation (CPR). The purpose of this cross-sectional study was to investigate long-term pain, lung function, physical function, and fracture healing after manual or mechanical CPR and in patients with and without flail chest. METHODS: Patients experiencing out-of-hospital cardiac arrest between 2013 and 2020 and transported to Sahlgrenska University Hospital were identified. Survivors who had undergone a computed tomography (CT) showing chest wall injury were contacted. Thirty-five patients answered a questionnaire regarding pain, physical function, and quality of life and 25 also attended a clinical examination to measure the respiratory and physical functions 3.9 (SD 1.7, min 2-max 8) years after the CPR. In addition, 22 patients underwent an additional CT scan to evaluate fracture healing. RESULTS: The initial CT showed bilateral rib fractures in all but one patient and sternum fracture in 69 %. At the time of the follow-up none of the patients had persistent pain, however, two patients were experiencing local discomfort in the chest wall. Lung function and thoracic expansion were significantly lower compared to reference values (FVC 14 %, FEV1 18 %, PEF 10 % and thoracic expansion 63 %) (p < 0.05). Three of the patients had remaining unhealed injuries. Patients who had received mechanical CPR in additional to manual CPR had a lower peak expiratory flow (80 vs 98 % of predicted values) (p=0.030) =0.030) and those having flail chest had less range of motion in the thoracic spine (84 vs 127 % of predicted) (p = 0.019) otherwise the results were similar between the groups. CONCLUSION: None of the survivors had long-term pain after CPR-related chest wall injuries. Despite decreased lower lung function and thoracic expansion, most patients had no limitations in physical mobility. Only minor differences were seen after manual vs. mechanical CPR or with and without flail chest.

Open Reduction and Internal Fixation for Supination-External Rotation Type IV Ankle Fractures by Means of Anterolateral and Posterolateral Approaches.

BACKGROUND: The present study aimed to analyze and compare the efficacy of the anterolateral and posterolateral approaches for surgical treatment of supination-external rotation type IV ankle fractures. METHODS: This retrospective study enrolled 60 patients (60 feet) with supination-external rotation type IV ankle fractures, including 30 patients (30 feet) treated by means of the anterolateral approach and 30 patients (30 feet) treated by means of the posterolateral approach. Postoperative clinical efficacy was compared between the groups based on operation time, intraoperative blood loss, postoperative complications, fracture healing time, visual analog scale scores, Short Form-36 Health Survey scores, and American Orthopedic Foot and Ankle Society scores. Comparisons between the two groups were performed using independent-samples t tests and analyses of variance. Intragroup differences were compared using paired t tests, and the χ2 test was used to compare categorical variables. RESULTS: All 60 included patients completed follow-up ranging from 12 to 18 months (mean duration, 14.8 ± 3.5 months). Although baseline characteristics were similar in the two groups, there were significant differences in operation time (86.73 ± 17.44 min versus 111.23 ± 10.05 min; P < .001) and intraoperative blood loss (112.60 ± 25.05 mL versus 149.47 ± 44.30 mL; P < .001). Although fracture healing time (10.90 ± 0.66 weeks versus 11.27 ± 0.94 weeks; P = .087) was shorter in the anterolateral group than in the posterolateral group, the difference was not significant. Postoperative complications occurred in one and three patients in the anterolateral and posterolateral approach groups, respectively. Visual analog scale scores were significantly lower in the anterolateral group than in the posterolateral group (1.43 ± 0.50 versus 1.83 ± 0.75; P = .019), although there was no significant difference in Short Form-36 Health Survey scores between the groups (73.63 ± 4.07 versus 72.70 ± 4.04; P = .377). However, American Orthopedic Foot and Ankle Society scores were higher in the anterolateral group than in the posterolateral group (80.43 ± 4.32 versus 75.43 ± 11.32; P = .030). CONCLUSIONS: Both the anterolateral and posterolateral approaches can achieve good results in the treatment of supination-external rotation type IV ankle fractures. Compared with the posterolateral approach, the anterolateral approach is advantageous for the treatment of supination-external rotation type IV ankle fractures given its safety and ability to reduce trauma, clear field of view revealed, and allow for exploration and repair of the inferior tibiofibular anterior syndesmosis within the same incision.

Technology Behind Cell Therapy Augmentation of Fracture Healing: Concentrated Bone Marrow Aspirate.

With an aging population, and an anticipated increase in overall fracture incidence, a sound understanding of bone healing and how technology can optimize this process is crucial. Concentrated bone marrow aspirate (cBMA) is a technology that capitalizes on skeletal stem and progenitor cells (SSPCs) to enhance the regenerative capacity of bone. This overview highlights the science behind cBMA, discusses the role of SSPCs in bone homeostasis and fracture repair, and briefly details the clinical evidence supporting the use of cBMA in fracture healing. Despite promising early clinical results, a lack of standardization in harvest and processing techniques, coupled with patient variability, presents challenges in optimizing the use of cBMA. However, cBMA remains an emerging technology that may certainly play a crucial role in the future of fracture healing augmentation.

A comparative study of volar locking-plate fixation with corticocancellous and pure cancellous bone grafts for scaphoid nonunion with dorsal intercalated segmental instability secondary to scaphoid humpback deformity.

INTRODUCTION: Bone grafts for scaphoid nonunion with deformity include cortcicocancellous or pure cancellous bone grafts. This study compared the outcomes between two types of bone grafts when employing a volar locking-plate in patients with scaphoid nonunion with dorsal intercalated segmental instability (DISI). PATIENTS AND METHODS: This retrospective study included 34 patients with scaphoid nonunion and DISI due to humpback deformity treated between March 2017 and January 2022. Two types of bone grafts were obtained from iliac crest. Twenty of the corticocancellous (CC) group underwent a wedge-shaped graft, while 14 patients of the pure cancellous (C-only) group received graft chips. In both groups, a 1.5-mm anatomically pre-contoured locking plate was used for fixation. Radiographic evaluations included the union rate and carpal alignment including scapholunate angle (SLA), radiolunate angle (RLA), intrascaphoid angle (ISA) and scaphoid height to length ratio (HLR). Clinical assessments encompassed wrist range-of-motion, grip strength, and patient-reported outcomes. RESULTS: Nineteen of the 20 patients in the CC group and 12 of the 14 patients in the C-only group respectively, achieving osseous union. The mean follow-up period in CC group was 14.7 (range, 12 ∼ 24) months and that in C-only group was 12.6 (range, 12 ∼ 15) months. Postoperatively, there were no significant intergroup differences of radiographic parameters including SLA (CC; 49.9° ± 6.7° vs. C-only; 48.9° ± 3.5°, P = 0.676), RLA (1.7° ± 6.4° vs. 2.4° ± 3.3°, P = 0.74), ISA (36° ± 7.5° vs. 36.6° ± 12.2°, P = 0.881), and HLR (0.54 ± 0.09 vs. 0.53 ± 0.05, P = 0.587). Clinical outcomes, including the flexion-extension arc (137° ± 30° vs. 158° ± 33°, P = 0.122), grip strength (93.4 % ± 15.4% vs. 99.5 % ± 16.7 %, P = 0.39), Quick Disabilities of the Arm, Shoulder, and Hand scores (11.2 ± 8.3 vs. 12.5 ± 7.7, P = 0.74) and Mayo Wrist Scores (81.2 ± 13.1 vs. 89 ± 11.4, P = 0.242) also showed no significant intergroup differences. CONCLUSIONS: Volar locking-plate fixation with pure cancellous bone grafts achieved outcomes comparable to those achieved with corticocancellous bone grafts in scaphoid nonunion with deformity, possibly due to the biomechanical advantages of the volar plate to provide structural supports.

Comparison of reamer irrigator aspirator (RIA) suspension versus bone marrow aspirate concentrate (BMC) for percutaneous treatment of long bone nonunions-A preclinical canine model.

OBJECTIVE: To compare the bone healing effects of percutaneously delivered bone marrow aspirate concentrate (BMC) versus reamer irrigator aspirator (RIA) suspension in a validated preclinical canine ulnar nonunion model. We hypothesized that BMC would be superior to RIA in inducing bone formation across a nonunion site after percutaneous application. The null hypothesis was that BMC and RIA would be equivalent. METHODS: A bilateral ulnar nonunion model (n= 6; 3 matched pairs) was created. Eight weeks after segmental ulnar ostectomy, RIA from the ipsilateral femur and BMC from the proximal humerus were harvested and percutaneously administered into either the left or right ulnar defect. The same volume (3 ml) of RIA suspension and BMC were applied on each side. Eight weeks after treatment, the dogs were euthanized, and the nonunions were evaluated using radiographic, biomechanical, and histologic assessments. RESULTS: All dogs survived for the intended study duration, formed radiographic nonunions 8 weeks after segmental ulnar ostectomy, and underwent the assigned percutaneous treatment. Radiographic and macroscopic assessments of bone healing at the defect sites revealed superior bridging-callous formation in BMC-treated nonunions. Histologic analyses revealed greater amount of bony bridging and callous formation in the BMC group. Biomechanical testing of the treated nonunions did not reveal any significant differences. CONCLUSION: Bone marrow aspirate concentrate (BMC) had important advantages over Reamer Irrigator Aspirator (RIA) suspension for percutaneous augmentation of bone healing in a validated preclinical canine ulnar nonunion model based on clinically relevant radiographic and histologic measures of bone formation.

Osteoimmunology of Fracture Healing.

PURPOSE OF REVIEW: The purpose of this review is to summarize what is known in the literature about the role inflammation plays during bone fracture healing. Bone fracture healing progresses through four distinct yet overlapping phases: formation of the hematoma, development of the cartilaginous callus, development of the bony callus, and finally remodeling of the fracture callus. Throughout this process, inflammation plays a critical role in robust bone fracture healing. RECENT FINDINGS: At the onset of injury, vessel and matrix disruption lead to the generation of an inflammatory response: inflammatory cells are recruited to the injury site where they differentiate, activate, and/or polarize to secrete cytokines for the purposes of cell signaling and cell recruitment. This process is altered by age and by sex. Bone fracture healing is heavily influenced by the presence of inflammatory cells and cytokines within the healing tissue.

Flexed position of the wrist in the cast reliably prevents displacement after physeal Salter-Harris I and II distal radius fractures.

BACKGROUND: Salter-Harris I and II fractures of the distal radius are common injuries. In our facility, immobilisation is performed in a way that counteracts angulation forces. The aim of our study was to determine whether there are significant differences between patients with and patients without a loss of reduction treated with this method and to determine what degree of flexion reliably prevents secondary displacement. PATIENTS AND METHODS: We conducted a retrospective study of 112 patients (mean age: 12 years) who had sustained a Salter-Harris type I or II fracture of the distal radius and were treated with reduction. Patients were grouped according to fracture type and whether they sustained a loss of reduction or not. Patients were compared for gender, age, initial angulation, angulation after reduction, degree of flexion/extension of the wrist in the cast, residual angulation, duration of immobilisation, and complication rate. We also analysed whether a 45-degree flexed position of the wrist in plaster provides reliable protection against secondary displacement. RESULTS: In group I, patients with no loss of reduction had a significantly greater degree of wrist flexion in the cast, a significantly shorter duration of immobilisation and significantly less residual angulation. Patients with an apex-volar deformity with the wrist immobilised at more than 45 degrees of flexion had no loss of reduction at all and had significantly less residual angulation compared with patients with the wrist immobilised at less than 45 degrees of flexion. In this patient group, loss of reduction was noted in 28% of cases. The patients in group II with loss of reduction showed a significantly higher angulation after the reduction. During the follow-up examination, one patient experienced physeal arrest followed by an ulnar impaction syndrome. Other complications recorded were minor. CONCLUSIONS: In summary, based on our results, we recommend that all physeal fractures of the distal radius with an apex-volar angulation can be safely treated with reduction and immobilisation counteracting the forces of angulation. For apex-dorsal fractures, palmar flexion of 45° allows for reliable reduction.

SVF Therapy of Delayed Fracture Union in Patients with Multiple Combat Injury. Case Report.

Delayed union of fractures is one of the most frequent complications in orthopedic practice, especially in polytrauma patients. With the development of new methods of regenerative medicine, including the use of adipose derived stromal cells as a component of the stromal-vascular fraction (SVF), new possibilities for conservative treatment of this problem have emerged. This article presents a clinical case of conservative treatment of delayed union of a radial bone fracture using local SVF injections. In the fracture space, SVF with PRP creates a pool of cells that could differentiate towards surrounding tissue, releases various inducers of tissue growth and, via an indirect chemotactic effect on receptors, mobilizes the body's own resources and creates conditions for angiogenesis and trophism in the injured segment. In the patient with delayed consolidation after SFV-therapy, progress in clinical and radiological dynamics was noted with complete healing within 7 months. The positive clinical result provides a basis for further study and implementation in practice.

Titanium versus stainless steel alloy bridge plates for distal femur fractures: Does callus form earlier with titanium?

INTRODUCTION: Distal femur fractures account for 3-6% of all femur fractures. Internal fixation of most distal femur fractures with an anatomic lateral locking plate should permit some motion at the metaphyseal portion of the fracture when secondary bone healing is planned by the operating surgeon. While several studies have been performed evaluating union rates for distal femur fractures with stainless steel and titanium plates, the timing of callus formation between stainless steel and titanium implants used as bridge plates for distal femur fractures (AO/OTA 33-A and -C) has been investigated to a lesser extent. We hypothesize that callus will be visualized earlier with post-operative radiographs with titanium versus stainless steel bridge plates. METHODS: We retrospectively reviewed a consecutive cohort of patients over 18 years of age with acute AO/OTA 33-A and 33-C fracture patterns treated with an isolated stainless steel or titanium lateral bridge plate within 4 weeks of injury by a single fellowship-trained orthopedic trauma surgeon from 2011 to 2020 at one academic Level 1 trauma center. An independent, fellowship-trained orthopedic trauma attending surgeon reviewed anterior-posterior (AP) and lateral radiographs from every available post-operative clinic visit and graded them using the Modified Radiographic Score for Tibia (mRUST). RESULTS: Twenty-five subjects were included in the study with 10 with stainless steel and 15 with titanium plates. There were no significant differences in demographics between both groups, including age, sex, BMI, injury classification, open versus closed, mechanism, and laterality. Statistically significant increased mRUST scores, indicating increased callus formation, were seen on 12-week radiographs (8.4 vs. 11.9, p = 0.02) when titanium bridge plates were used. There were no statistically significant differences in mRUST scores at 6 or 24-weeks, but scores in the titanium group were higher in at every timepoint. DISCUSSION: In conclusion, we observed greater callus formation at 12 weeks after internal fixation of 33-A and 33-C distal femur fractures treated with titanium locked lateral distal femoral bridge plates compared to stainless steel plates. Our data suggest that titanium metallurgy may have quicker callus formation compared to stainless steel if an isolated, lateral locked bridge plate is chosen for distal femur fracture fixation.

Increased ß2-adrenergic signaling promotes fracture healing through callus neovascularization in mice.

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the ß2-adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine. In a murine model of femoral osteotomy combined with cortical impact brain injury, TBI was associated with ADRB2-dependent enhanced fracture healing compared with osteotomy alone. In the unfractured 12-week-old mouse skeleton, ADRB2 was required for TBI-induced decrease in bone formation and increased bone resorption. Adult 30-week-old mice had higher bone concentrations of norepinephrine, and ADRB2 expression was associated with decreased bone volume in the unfractured skeleton and better fracture healing in the injured skeleton. Norepinephrine stimulated expression of vascular endothelial growth factor A and calcitonin gene-related peptide-α (αCGRP) in periosteal cells through ADRB2, promoting formation of osteogenic type-H vessels in the fracture callus. Both ADRB2 and αCGRP were required for the beneficial effect of TBI on bone repair. Adult mice deficient in ADRB2 without TBI developed fracture nonunion despite high bone formation in uninjured bone. Blocking ADRB2 with propranolol impaired fracture healing in mice, whereas the ADRB2 agonist formoterol promoted fracture healing by regulating callus neovascularization. A retrospective cohort analysis of 72 patients with long bone fractures indicated improved callus formation in 36 patients treated with intravenous norepinephrine. These findings suggest that ADRB2 is a potential therapeutic target for promoting bone healing.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.