Direct Mapping of Cytomechanical Homeostasis Destruction in Osteoarthritis Based on Silicon Nanopillar Array.

Osteoarthritis (OA) is the most prevalent joint degenerative disease characterized by chronic joint inflammation. The pathogenesis of OA has not been fully elucidated yet. Cartilage erosion is the most significant pathological feature in OA, which is considered the result of cytomechanical homeostasis destruction. The cytomechanical homeostasis is maintained by the dynamic interaction between cells and the extracellular matrix, which can be reflected by cell traction force (CTF). It is critical to assess the CTF to provide a deeper understanding of the cytomechanical homeostasis destruction and progression in OA. In this study, a silicon nanopillar array (Si-NP) with high spatial resolution and aspect ratio is fabricated to investigate the CTF in response to OA. It is discovered that the CTF is degraded in OA, which is attributed to the F-actin reorganization induced by the activation of RhoA/ROCK signaling pathway. Si-NP also shows promising potential as a mechanopharmacological assessment platform for OA drug screening and evaluation.

Hierarchical hydrogel scaffolds with a clustered and oriented structure.

Hydrogel scaffolds play a critical role in tissue engineering due to their hydrophilic network structure and good biocompatibility. Constructing anisotropic scaffolds geometrically similar to injured tissues is conducive to promoting the generation of tissue and organ equivalents, or to guiding and enhancing the regeneration of injured tissues. In this study, we developed polyvinyl alcohol (PVA)/alginate hierarchical hydrogel scaffolds with a clustered and oriented structure using a method that combines directional freezing and drying under stretching. Our hydrogel scaffolds with an adjustable modulus (50 kPa-20 MPa) can match different types of injured tissues. The clustered and oriented structure successfully guided the alignment and orientation of fibroblasts and chondrocytes. This work provides a new idea for constructing hydrogels with hierarchical and anisotropic microstructures, which have promising applications in tissue regeneration.

The effect of hamstring donor-site block for functional outcomes and rehabilitation after anterior cruciate ligament reconstruction.

Purpose: To determine the effect of local infiltration anesthesia (LIA) at the donor site combined with a femoral nerve block (FNB) on short-term postoperative pain, functional outcomes, and rehabilitation after arthroscopic hamstring tendon autograft anterior cruciate ligament reconstruction (ACLR). Methods: This study was a single center, randomized controlled trial. Seventy-three subjects with ACL rupture were enrolled. Participants were randomly allocated to two groups, 47 in the experimental group (Group A) and 26 in the control group (Group B). All operations were performed under FNB. In Group A, 10 ml of 1% ropivacaine was injected precisely at the hamstring donor site. Patients in Group B were treated with the same amount of saline. Preoperatively and postoperatively, pain scores based on the numerical rating scale (NRS) and consumption of opioids were recorded. In addition, knee functions were assessed by the International Knee Documentation Committee Subjective Knee Form (IKDC), the Lysholm score, and the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and postoperatively at 1 and 3 months. In addition, we applied the KNEELAX3 arthrometer to evaluate the stability of the knee preoperatively and postoperatively so that subjective and objective knee conditions were obtained to help us assess knee recovery in a comprehensive manner. Results: The hamstring donor-site block reduced pain within the first 12 postoperative hours. There were no significant differences between two groups in pain intensity preoperatively and equal to or greater than 24 hours postoperatively. Furthermore, there were no differences between the groups concerning knee functions preoperatively or in the short-term follow-up at 1 and 3 months. Conclusion: LIA at the donor site can effectively improve the early postoperative pain of patients after ACLR and reduce the use of opioids without affecting the functional outcomes of the surgery.

Combination of external fixation using digital six-axis fixator and internal fixation to treat severe complex knee deformity.

BACKGROUND: Severe knee valgus/varus or complex multiplanar deformities are common in clinic. If not corrected in time, cartilage wear will be aggravated and initiate the osteoarthritis due to lower limb malalignment. Internal fixation is unable to correct severe complex deformities, especially when combined with lower limb discrepancy (LLD). Based on the self-designed digital six-axis external fixator Q spatial fixator (QSF), which can correct complex multiplanar deformities without changing structures, accuracy of correction can be improved significantly. METHODS: This retrospective study included 24 patients who suffered from complex knee deformity with LLD treated by QSF and internal fixation at our institution from January 2018 to February 2021. All patients had a closing wedge distal femoral osteotomy with internal fixation for immediate correction and high tibia osteotomy with QSF fixation for postoperative progressive correction. Data of correction prescriptions were computed by software from postoperative CT scans. RESULTS: Mean discrepancy length of operative side was 2.39 ± 1.04 cm (range 0.9-4.4 cm) preoperatively. The mean difference of lower limb was 0.32 ± 0.13 cm (range 0.11-0.58 cm) postoperatively. The length of limb correction had significant difference (p < 0.05). The mean MAD and HKA decreased significantly (p < 0.05), and the mean MPTA and LDFA increased significantly (p < 0.05). There were significant increase (p < 0.05) in the AKSS-O, AKSS-F and Tegner Activity Score. The lower limb alignment was corrected (p < 0.05). The mean time of removing external fixator was 112.8 ± 17.9 days (range 83-147 days). CONCLUSIONS: Complex knee deformity with LLD can be treated by six-axis external fixator with internal fixation without total knee arthroplasty. Lower limb malalignment and discrepancy can be corrected precisely and effectively by this approach.

A Retrospective Study of the Perioperative Period Management of Joint Arthroplasty in Patients with Chronic Kidney Disease.

OBJECTIVE: With the rising prevalence of chronic kidney disease (CKD) and the increasing demand for joint arthroplasty, the management of CKD patients in the perioperative period of joint arthroplasty has become an issue worthy of attention for orthopedic surgeons. This study aimed to explore comprehensive perioperative period management strategies for CKD patients. METHODS: From March 2017 to August 2022, 62 patients who underwent joint arthroplasty in our hospital were included in a retrospective study, including 31 CKD patients (mean age 69.8 ± 13.4 years old) and 31 non-CKD patients (mean age 69.4 ± 14.2 years old). The outcome indicators were analyzed, including serum urea, serum creatinine, blood uric acid, hematocrit, and hemoglobin. RESULTS: All patients included in the retrospective study had an average preoperative preparation time of 4.3 ± 2.6 days and an average hospitalization time of 11.0 ± 7.3 days. There were no significant differences in the changes in the serum urea values between the preoperative and postoperative measurements in the CKD patients or in the serum creatinine values and blood uric acid values (P > 0.05). The hemoglobin value in postoperative measurements was lower than in preoperative measurements in the CKD patients (P < 0.05). The hematocrit value in postoperative measurements was lower than in preoperative measurements in the CKD patients (P < 0.001). CONCLUSION: Patients with CKD have distinct characteristics compared to non-CKD patients, and they generally have a higher risk for postoperative complications and adverse events. Recognition of risk factors, suitable timing of surgery, the undertaking of protective strategies, and proper management of complications are vital for managing CKD patients in the perioperative period of joint arthroplasty.

OPN inhibits autophagy through CD44, integrin and the MAPK pathway in osteoarthritic chondrocytes.

Background: To investigate whether osteopontin (OPN) affects autophagy in human osteoarthritic chondrocytes and determine the roles of CD44, αvß3 integrin and the Mitogen-activated protein kinase (MAPK) pathway in this progress. Methods: First, we compared the autophagy levels in the human osteoarthritis (OA) and normal cartilage, then, we cultured human OA chondrocytes in vitro and treated cells with recombinant human OPN (rhOPN) to determine autophagy changes. Next, the anti-CD44 and anti-CD51/61 monoclonal antibodies (Abs) or isotype IgG were used to determine the possible role of CD44 and αvß3 integrin; subsequently, an inhibitor of the ERK MAPK pathway was used to investigate the role of ERK MAPK. Western blotting was used to measure the Beclin1, LC3 II and MAPK proteins expressions, mRFP-GFP-LC3 confocal imaging and transmission electron microscopy were also used to detect the autophagy levels. Cell Counting Kit-8 (CCK-8) was used to assay the proliferation and activity of chondrocytes. Results: The LC3 protein was greatly decreased in OA cartilage compared to normal cartilage, and OPN suppressed the autophagy activity in chondrocytes in vitro. Blocking experiments with anti-CD44 and anti-CD51/61 Abs indicated that OPN could suppress the expression of LC3II and Beclin1 through αvß3 integrin and CD44. Our results also indicated that the ratio of p-ERK/ERK but not p-P38/P38 and p-JNK/JNK was increased after the rhOPN treatment. The ERK inhibitor inhibited the activity of OPN in the suppression of autophagy, and the CCK-8 results showed that rhOPN could promote chondrocyte proliferation. Conclusion: OPN inhibited chondrocyte autophagy through CD44 and αvß3 integrin receptors and via the ERK MAPK signaling pathway.

The role and therapeutic potential of stem cells in skeletal muscle in sarcopenia.

Sarcopenia is a common age-related skeletal muscle disorder featuring the loss of muscle mass and function. In regard to tissue repair in the human body, scientists always consider the use of stem cells. In skeletal muscle, satellite cells (SCs) are adult stem cells that maintain tissue homeostasis and repair damaged regions after injury to preserve skeletal muscle integrity. Muscle-derived stem cells (MDSCs) and SCs are the two most commonly studied stem cell populations from skeletal muscle. To date, considerable progress has been achieved in understanding the complex associations between stem cells in muscle and the occurrence and treatment of sarcopenia. In this review, we first give brief introductions to sarcopenia, SCs and MDSCs. Then, we attempt to untangle the differences and connections between these two types of stem cells and further elaborate on the interactions between sarcopenia and stem cells. Finally, our perspectives on the possible application of stem cells for the treatment of sarcopenia in future are presented. Several studies emerging in recent years have shown that changes in the number and function of stem cells can trigger sarcopenia, which in turn leads to adverse influences on stem cells because of the altered internal environment in muscle. A better understanding of the role of stem cells in muscle, especially SCs and MDSCs, in sarcopenia will facilitate the realization of novel therapy approaches based on stem cells to combat sarcopenia.

Macrophage Polarization Modulated by NF-κB in Polylactide Membranes-Treated Peritendinous Adhesion.

Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.

Effects of Platelet-Rich Plasma and Bone Marrow Mesenchymal Stem Cells on Meniscal Repair in the White-White Zone of the Meniscus.

OBJECTIVE: To investigate the role of autologous platelet-rich plasma (PRP) on the repair of meniscal white-white zone injury through promoting the proliferation of canine bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: A total of 24 beagle dogs were selected to construct meniscal white-white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage. RESULTS: Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P < 0.05), and there was no significant difference between the PRP group and the PRP + BMSCs group (P > 0.05). All subjects were divided into the non-healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non-healing group than that in the healing group. CONCLUSION: The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white-white zone injury.

Simulated operation combined with patient-specific instrumentation technology is superior to conventional technology for supramalleolar osteotomy: a retrospective comparative study.

OBJECTIVE: Over the past seven years, our team has designed a simulated operation combined with patient-specific instrumentation (SO-PSI) assisted supramalleolar osteotomy (SMOT) method and applied it in the clinic. This study aimed to evaluate the differences between SO-PSI technology and conventional operation (CO) technology for SMOT in preoperative planning, intraoperative application, and postoperative curative effect. METHODS: We retrospectively analyzed SMOT data collected from our hospital between October 2014 and December 2018. Patients (n = 28) were enrolled and divided into CO (n = 17) and SO-PSI (n = 11) groups; mean follow-up time was 33.4 (range, 13 to 59) months. We statistically analyzed and compared perioperative data, accuracy of preoperative planning, intraoperative application, difference between pre- and post-operative radiologic ankle angles, changes in American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, range of ankle motion, and Takakura stage after surgery. RESULTS: All ankle alignments and positions were recovered for both groups. Compared with the CO group, the SO-PSI group had a shorter mean operating time and postoperative hospital stay, a decreased number of fluoroscopy examinations, lower albumin reduction, longer preoperative planning time and preoperative hospital stay, and increased hospitalization expenses. In the SO-PSI group, comparison of ankle angles at preoperative planning and postoperatively revealed good correlation, while this was not the case in the CO group. Mean tibial ankle center discrepancy for the SO-PSI group was 1.86 ± 1.06 mm. On follow-up, all radiologic parameters for the two groups improved significantly; however, the improvement of the tibial anterior surface angle and tibiotalar tilt angle for the SO-PSI group were more obvious than those for the CO group. AOFAS score, VAS score, ankle range of motion, and Takakura stage improved after surgery in both groups; however, the improvements in the SO-PSI group were greater than those in the CO group overall. CONCLUSIONS: SO-PSI technology can facilitate accurate and rapid preoperative planning for SMOT. In general, compared with conventional technology, SO-PSI has advantages for preoperative planning, intraoperative application, and postoperative curative effect.

The effects of posterior cruciate ligament rupture on the biomechanical and histological characteristics of the medial collateral ligament: an animal study.

BACKGROUND: To investigate the effect of complete rupture of the posterior cruciate ligament (PCL) on the biomechanics and histology of the medial collateral ligament (MCL). MATERIALS AND METHODS: Seventy-two male rabbits were randomly divided into two groups: the ruptured group was treated with complete PCL amputation, while the intact group was only subjected to PCL exposure without amputation. Eighteen rabbits were randomly sacrificed at 8, 16, 24, and 40 weeks after the operation, and their specimens were processed for mechanical tensile testing, nano-indentation experiments, hematoxylin-eosin (HE) staining, and picrosirius-polarization staining. RESULTS: There was no significant difference in the length and maximum displacement of the MCL between the ruptured group and the intact group at each time point. The maximum load of the ruptured group was significantly smaller than that of the intact group at 40 W. The elastic modulus and micro-hardness of the ruptured group increased significantly at 24 W and decreased significantly at 40 W. At 16 W and 24 W after PCL rupture, the number of type I collagen fibers and type III collagen fibers in the MCL of the ruptured group was significantly increased compared with that of the intact group. While the type I collagen fibers of the ruptured group were significantly decreased compared with the intact group at 40 W, there was no significant difference in type III collagen fibers between the ruptured group and the intact group. CONCLUSION: PCL rupture has no significant effect on the mechanical and histological properties of MCL in a short period of time under physiological loading, but the histological and mechanical properties of MCL decrease with time.

Mouse models of sarcopenia: classification and evaluation.

Sarcopenia is a progressive and widespread skeletal muscle disease that is related to an increased possibility of adverse consequences such as falls, fractures, physical disabilities and death, and its risk increases with age. With the deepening of the understanding of sarcopenia, the disease has become a major clinical disease of the elderly and a key challenge of healthy ageing. However, the exact molecular mechanism of this disease is still unclear, and the selection of treatment strategies and the evaluation of its effect are not the same. Most importantly, the early symptoms of this disease are not obvious and are easy to ignore. In addition, the clinical manifestations of each patient are not exactly the same, which makes it difficult to effectively study the progression of sarcopenia. Therefore, it is necessary to develop and use animal models to understand the pathophysiology of sarcopenia and develop therapeutic strategies. This paper reviews the mouse models that can be used in the study of sarcopenia, including ageing models, genetically engineered models, hindlimb suspension models, chemical induction models, denervation models, and immobilization models; analyses their advantages and disadvantages and application scope; and finally summarizes the evaluation of sarcopenia in mouse models.

The role of melatonin in sarcopenia: Advances and application prospects.

Sarcopenia is an age-related disease that has gradually become a serious health problem for elderly individuals. It not only greatly increases the risk of falls, weakness, and disability but also reduces the ability of patients to take care of themselves. Sarcopenia can directly affect the quality of life and disease prognosis of elderly individuals. However, drug interventions for this disease are lacking. Melatonin is a biological hormone produced by the body that has good free radical scavenging effects, antioxidant effects and other effects. It was originally used as a sleep aid and is now being used for an increasing number of new indications. Its effect on sarcopenia has also begun to attract attention. It is currently known that it can protect the mitochondria of skeletal muscle cells, maintain the number of muscle fibres, partially reverse the pathological changes of ageing muscle tissue, and increase muscle strength in patients with sarcopenia. A large number of microRNAs are expressed during cell ageing, that in turn provides a biological background to age-related diseases, like sarcopenia. Increasing studies have found an interaction between melatonin and miRNAs, suggesting that melatonin can be used in the treatment of sarcopenia. The increased expression of inflammation-associated miRNA-483 in elderly patients may be the basis for the age-dependent decrease in melatonin secretion，that may play a role in the morbidity of sarcopenia. Melatonin is closely related to sarcopenia. It has a wide range of effects on sarcopenia and has good application prospects for the prevention and treatment of sarcopenia.

The therapeutic effects of earthworm extract on deep second-degree burn wound healing.

BACKGROUND: To investigated the effect of earthworm extract (EE) on deep second-degree burn wound healing process. METHODS: A burn wound model was created on the mice's skin and was subject to different treatments: the control group received no treatment; the Jingwanhong (JWH: a well-established, widely used external ointment for treating burn wounds) group was treated with 0.1 g of JWH cream and spray it on the wound surface; the EE group was treated with 0.1 mL of EE solution. All the mice were sacrificed at 3, 7, 11, and 15 days after injury (n=6/group/time point). Macroscopic observation, wound healing rate (WHR), wound healing time (WHT), water content (WC), hydroxyproline (Hyp) content, histological, and hematological analyses were performed at the burn wound sites. RESULTS: Better, faster burn wound healing in the JWH and EE groups than the control group at 15 days after injury were detected at the wound sites. Compared to the control group, the EE group had higher WHR, shorter WHT, lower WC, higher Hyp content, more fibroblasts, fibrocytes, and capillary endothelial cells; in addition, they showed greater capillary endothelial cell grouping at the wound sites during the healing process. This group also showed more platelets, white blood cells (WBCs), and neutrophilic granulocytes in serum at the early stages after burn injury. CONCLUSIONS: EE could effectively promote skin wound healing by decreasing edema, suppressing fibrosis, activating angiogenesis and epithelial regeneration, inhibiting scar formation, and reducing the risk of infection. Thus, it could be made into a promising healing agent for burn wound.

Effects of earthworm extract on the lipid profile and fatty liver induced by a high-fat diet in guinea pigs.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), characterized by the accumulation of excess fat in the liver in people who consume little or no alcohol, is becoming increasingly common around the world, especially in developed countries. Extracts from earthworms have been used as alternative therapies for a variety of diseases but not in NAFLD. Therefore, the aim of this study was to investigate the effect of earthworm extract (EE) on diet-induced fatty liver disease in guinea pigs. METHODS: EE was extracted, and the effect of EE on the lipid levels and liver damage in guinea pigs fed a high-fat diet (HFD) was assessed. Thirty male guinea pigs at 3 weeks of age were allocated equally to five groups, namely, chow diet, HFD, and HFD with different dosages (0.3, 1.4 and 6.8 µg per kg bodyweight per day) of EE for 4 weeks, and their body weight was monitored throughout the experiment. Liver tissues were examined for gross morphology and histology. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate aminotransferase (AST) were determined using an autoanalyser. RESULTS: HFD induced NAFLD in guinea pigs. HFD-fed guinea pigs that received EE treatment showed milder increases in the serum levels of TC, TG and LDL-C, as well as in the body weight growth rate, compared to the HFD group without EE supplementation. EE intervention reduced the number of lipid-containing hepatocytes, hepatocellular ballooning and sinusoidal distortion in the liver in HFD-fed animals. ALT in serum was significantly elevated by HFD. No statistically significant difference in ALT levels was found between the chow diet group and the HFD group with EE treatment. CONCLUSIONS: This study demonstrates that the administration of EE suppressed the induction of serum TC, TG and LDL-C in response to HFD. EE also reduced liver damage in HFD-fed guinea pigs. These findings suggest that EE has alleviating effects on dyslipidaemia and liver damage associated with NAFLD.

Myogenic Differentiation of Stem Cells for Skeletal Muscle Regeneration.

Stem cells have become a hot research topic in the field of regenerative medicine due to their self-renewal and differentiation capabilities. Skeletal muscle tissue is one of the most important tissues in the human body, and it is difficult to recover when severely damaged. However, conventional treatment methods can cause great pain to patients. Stem cell-based tissue engineering can repair skeletal muscle to the greatest extent with little damage. Therefore, the application of stem cells to skeletal muscle regeneration is very promising. In this review, we discuss scaffolds and stem cells for skeletal muscle regeneration and put forward our ideas for future development.

Characterization of the Subchondral Bone and Pain Behavior Changes in a Novel Bipedal Standing Mouse Model of Facet Joint Osteoarthritis.

BACKGROUND: The subchondral bone parallels with the progression of osteoarthritis (OA). However, the biomechanical properties and histopathological changes of subchondral bone changes in the lumbar facet joint (LFJ) after long-term axial loading on the spine have not been explored. In this study, we aimed to investigate the subchondral bone histopathological changes that occur in the LFJ and pain behaviors in a novel bipedal standing mouse model. METHODS: Sixteen 8-week-old male C57BL/6 mice were randomly assigned into bipedal standing and control groups. A finite element stimulate model based on the micro-CT data was generated to simulate the von Mises stress distribution on the LFJ during different positions. The spine pain behaviors tests were analysis. In addition, the change in the subchondral bone of the LFJ was assessed by histological and immunohistochemistry staining. RESULTS: The computerized simulation of the von Mises stress distribution in the superior articular process of LFJ at the spine level 5 in the lying position increased and reached a maximum value at the bipedal standing posture. The spine pain behavior test revealed that the threshold of pressure tolerance decreased significantly in bipedal groups relative to control groups, whereas the mechanical hyperalgesia of the hind paw increased significantly in bipedal groups relative to control groups. The axial load accelerates LFJ degeneration with increased histological scores in bipedal groups. The expression of type II collagen and aggrecan (ACAN) was significantly decreased in the bipedal groups compared with the control groups, whereas the expression of MMP13 was increased. Compared with the control groups, the osteoclast activity was activated with higher TRAP-positive staining and associated with increased CD-31-positive vessels and GCRP-positive nerve ending expression in the subchondral bone of LFJ. CONCLUSION: Collectively, long-term axial loading induces the development of spine hyperalgesia in mice associate with increased osteoclast activity and aberrant angiogenesis and nerve invasion into the subchondral bone of LFJ that stimulates the natural pathological change in human LFJ OA. These results indicate that aberrant bone remodeling associate with aberrant nerve innervation in the subchondral bone has a potential as a therapeutic target in LFJ OA pain.