The purpose of the in vivo Animal model & histology core is to consolidate key personnel and equipment to provide a centralized facility that will enhance collaborative and multidisciplinary investigations into multiple mechanisms in age related skeletal degenerative disease. Core B will serve as a center to realize an optimized and reasonable utilization and allocation of experimental and human resources. Employing skillful personnel to conduct the common procedures in a standardized manner is not only a cost- and time-efficient strategy but also can maximally reduce the potential for bias and increase the scientific rigor. Ranging from tissue histological analysis to functional behavior test, Core B will facilitate the investigation of age related skeletal degenerative diseases from four aspects: 1. Animal models and microsurgeries. The proposed surgical animal models: destabilization of the medial meniscus (DMM), lumbar spine instability (LSI), dorsal root ganglion (DRG) exposure for in vivo imaging will be conducted in the Core B. Our core will set up a team with members who have extensive experience in conducting complicated microsurgeries in small animals. 2. Histological grading. Core B will perform histological grading based on the Safranin O/fast green and H&E staining. The osteoarthritis research society international (OARSI) scoring system will be applied to assess the joint degenerative status while the grading method for classification of age-related changes in lumbar intervertebral discs will be used to determine the degenerative status of lumbar discs. 3. Micro-CT analysis. Micro-CT measurements will be done in excised lumbar vertebrae and knee joints to determine the individual volumetric, densitometric and 3- dimensional microarchitecture of subchondral bone or endplate. These parameters are essential for investigating the biomechanical impact of subchondral bone on articular cartilage or endplate on intra-vertebral discs. 4: Behavior test. To better translate the preclinical results into clinical settings, behavior test will be applied to all the 4 projects within this PPG program. Core B will perform gait analysis, Von Frey test, Mechanical hyperalgesia and cold sensitivity test for individual projects. To reduce the variability that potentially generated because of the changes of environment, the different handling of animals, Core B will designate well trained personnel in charging of the animal behavioral tests and equipment/facility management. 5. Training. The Core will train and maintain the continuing education of a key laboratory person from each project to help perform the routine histological, behavior and micro-CT analysis.