Effect of carpometacarpal joint osteoarthritis, sex, and handedness on thumb in vivo kinematics.

PURPOSE: To investigate the influence of trapeziometacarpal (TMC) osteoarthritis (OA) on the 3-dimensional motion capability of the TMC and thumb metacarpophalangeal (MCP) joints. In order to examine other factors affecting the thumb's motion kinematics, we further aimed to address the influence of sex and handedness on the motion capability of normal TMC and MCP joints. METHODS: We included 18 healthy subjects (9 women, 9 men; 8 dominant hands, 10 nondominant hands) and 18 women with stage II/III TMC OA. A motion analysis system using surface markers was used to quantify the thumb's 3-dimensional opposition-reposition kinematics. The range of motion of the thumb's TMC and MCP joints in flexion-extension, abduction-adduction, and pronation-supination were determined. RESULTS: TMC OA led to a loss in abduction-adduction in the TMC joint (38° in controls, 26° in TMC OA subjects), although neither flexion-extension nor pronation-supination were affected. At the MCP joint, the TMC OA subjects showed a 48% reduction in abduction-adduction (32° controls, 16° TMC OA subjects) and 42% reduction in pronation-supination (34° in controls, 20° in TMC OA subjects) than the healthy controls. Ranges of motion of the healthy TMC and MCP joints were similar in dominant and nondominant hands as well as in women and men. DISCUSSION: The study demonstrated that stage II/III TMC OA restricts the motion of the TMC joint in abduction-adduction and of the MCP joint in abduction-adduction and pronation-supination. Thumb motion capability was unaffected by sex and handedness. CLINICAL RELEVANCE: Osteoarthritis-induced loss of TMC motion did not reflect a generalizable clinical parameter, rather, it seemed to distinctly affect the TMC and the MCP joints and their motion planes and directions. As neither sex nor handedness influenced the motion capabilities of the healthy thumb, kinematic factors contributing to TMC OA may develop at a later age.

Effect of whole-body vibration and insulin-like growth factor-I on muscle paralysis-induced bone degeneration after botulinum toxin injection in mice.

Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone degradation with substantial bone loss. We hypothesized that whole-body vibration (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis-induced bone degradation following BTX injections by activation of the protein kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I, BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous injections of human IGF-I (1 µg/day). The BTX+WBV and BTX+WBV+IGF-I groups underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks. Femora were scanned by pQCT, and mechanical properties were determined. On tibial sections TRAP staining, static histomorphometry, and immunohistochemical staining against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were conducted. BTX injection decreased trabecular and cortical bone mineral density. The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings were not differentially altered in the injected hind limbs between groups. We found that high-frequency, low-magnitude WBV can counteract paralysis-induced bone loss following BTX injections, while we could not detect any effect of treatment with IGF-I.

Doxycycline-induced expression of transgenic human tumor necrosis factor α in adult mice results in psoriasis-like arthritis.

OBJECTIVE: To generate doxycycline-inducible human tumor necrosis factor α (TNFα)-transgenic mice to overcome a major disadvantage of existing transgenic mice with constitutive expression of TNFα, which is the limitation in crossing them with various knockout or transgenic mice. METHODS: A transgenic mouse line that expresses the human TNFα cytokine exclusively after doxycycline administration was generated and analyzed for the onset of diseases. RESULTS: Doxycycline-inducible human TNFα-transgenic mice developed an inflammatory arthritis- and psoriasis-like phenotype, with fore and hind paws being prominently affected. The formation of "sausage digits" with characteristic involvement of the distal interphalangeal joints and nail malformation was observed. Synovial hyperplasia, enthesitis, cartilage and bone alterations, formation of pannus tissue, and inflammation of the skin epidermis and nail matrix appeared as early as 1 week after the treatment of mice with doxycycline and became aggravated over time. The abrogation of human TNFα expression by the removal of doxycycline 6 weeks after beginning stimulation resulted in fast resolution of the most advanced macroscopic and histologic disorders, and 3-6 weeks later, only minimal signs of disease were visible. CONCLUSION: Upon doxycycline administration, the doxycycline-inducible human TNFα-transgenic mouse displays the major features of inflammatory arthritis. It represents a unique animal model for studying the molecular mechanisms of arthritis, especially the early phases of disease genesis and tissue remodeling steps upon abrogation of TNFα expression. Furthermore, unlimited crossing of doxycycline-inducible human TNFα-transgenic mice with various knockout or transgenic mice opens new possibilities for unraveling the role of various signaling molecules acting in concert with TNFα.